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Shifts in the light-dark cycle increase unpredictability of the cardiovascular system
Abstract
Physiological variables such as heart rate (HR) and blood pressure (BP) exhibit long-term circadian rhythms, which can be disturbed by shift work. On the other hand, short-term oscillations in HR and BP have a high prognostic value. Therefore, we aimed to determine if the short-term variability, complexity and entropy of HR and BP would be affected by a regular light/dark (LD) cycle and phase delay shifts of the LD cycle, leading to chronodisruption. Telemetry-monitored rats were exposed first to the regular LD cycle and then to shifts in LD for 8 weeks. On the basis of long-term HR and BP recording and evaluation, we found circadian rhythms in HR and BP variability, complexity and entropy under regular LD cycles. Short-term exposure to shifts disturbed circadian rhythms of HR and BP variability, complexity and entropy, indicating chronodisruption. The power of circadian rhythms was suppressed after 8 weeks of phase delay shifts. Long-term exposure to shifts increased variability (p = 0.007), complexity (p < 0.001) and dark-time entropy (p = 0.006) of HR but not BP. This is the first study demonstrating long-term recording and estimation of HR and BP variability, complexity and entropy in conscious rats exposed to irregular lighting conditions. After long-term phase delay shifts, short-term variability of HR was less predictable than in controls. This study suggests that changes in short-term HR and BP oscillations induced by long-term shift work can negatively affect cardiovascular health.
... Hz), and high frequency (HF; 0.75-2.5 Hz). The index of cardiac sympathovagal balance was evaluated from the low-to-high frequency ratio (LF/HF) [13,14], and the spontaneous baroreflex sensitivity (BRS) as α-index from heart rate and BP LFs (LF HR /LF BP )^0.5 [15,16]. ...
... In normotensive HanSDc, the sympathovagal balance (indicated by LF/HF) decreased significantly with age. However, we did not observe such a decrease in TGRc offspring during the dark (active) phase, indicating their SNA was excessively elevated [13]. This is further supported by the observation that TGR exhibit higher hypothalamic norepinephrine turnover in the dark phase [28]. ...
Aldosterone regulates blood pressure (BP) through water and sodium balance. In our study, we studied if continuous treatment with a mineralocorticoid receptor antagonist, spironolactone (30 mg/kg/day) for 20 days can: 1) attenuate hypertension development and restore inverted 24-h BP rhythm in hypertensive transgenic (mRen-2)27 rats (TGR) measured by telemetry; 2) improve function of the kidneys and heart; 3) be protective against high salt load (1% in water) by mitigating oxidative injury and improving kidney function. Spironolactone decreased albuminuria and 8-isoprostane in normal and salt load conditions in BP-independent effects. Salt load increased BP, impaired autonomic balance, suppressed plasma aldosterone level and increased natriuresis, albuminuria and oxidative injury in TGR. Spironolactone did not restore the inverted 24-h rhythm of BP in TGR, therefore, mineralocorticoids are not crucial in regulation of BP daily profile. Spironolactone improved kidney function, decreased oxidative stress and was protective against high salt load in the BP-independent manner.
... Analysing Fig. 1 Beat-to-beat, minute-to-minute, hour-to-hour, and circadian blood pressure variability reflect the activity of specific regulatory systems this data using spectral, attractor or nonlinear analysis methods can take time and effort. However, based on the analysis, it is known that blood pressure variability is not random; it follows its internal laws, regularity, and thus predictability, which we should fully understand [7]. Studying the variability of physiological variables can help predict the future state of physiological systems and even anticipate diseases before changes happen on the biochemical, anatomical and morphological levels. ...
... In humans and nocturnal rats, it is likely that ALAN [30,82], as well as phase shifts of the light-dark regime [57], can alter the sympathovagal balance, which is manifested by increased sympathetic activity in humans and, conversely, decreased sympathetic activity in rats. ...
Artificial light at night (ALAN) affects most of the population. Through the retinohypothalamic tract, ALAN modulates the activity of the central circadian oscillator and, consequently, various physiological systems, including the cardiovascular one. We summarised the current knowledge about the effects of ALAN on the cardiovascular system in diurnal and nocturnal animals. Based on published data, ALAN reduces the day-night variability of the blood pressure and heart rate in diurnal and nocturnal animals by increasing the nocturnal values of cardiovascular variables in diurnal animals and decreasing them in nocturnal animals. The effects of ALAN on the cardiovascular system are mainly transmitted through the autonomic nervous system. ALAN is also considered a stress-inducing factor, as glucocorticoid and glucose level changes indicate. Moreover, in nocturnal rats, ALAN increases the pressure response to load. In addition, ALAN induces molecular changes in the heart and blood vessels. Changes in the cardiovascular system significantly depend on the duration of ALAN exposure. To some extent, alterations in physical activity can explain the changes observed in the cardiovascular system after ALAN exposure. Although ALAN acts differently on nocturnal and diurnal animals, we can conclude that both exhibit a weakened circadian coordination among physiological systems, which increases the risk of future cardiovascular complications and reduces the ability to anticipate stress.
... Reduced amplitude of ion rhythms, or their temporal misalignment with sympathetic stimulation, will attenuate the intrinsic capacity of cardiomyocytes to facilitate increased heart rate at this time. For humans, we propose that dysregulation of cardiac ion or protein rhythms, during shift work or aging, renders the heart less competent to satisfy increased output demand in the early morning, contributing to the increased frequency of adverse events at this time [80][81][82][83][84][85] . ...
Between 6–20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na⁺, K⁺, and Cl⁻ through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes confer daily variation in electrical activity. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.
... Esto se ha asociado con la sensación de pérdida del sentido del tiempo y el uso incrementado de dispositivos digitales 4 Asimismo, experimentan mayores niveles de estrés relacionados con la exposición continua a las noticias mundiales sobre las repercusiones económicas y laborales de la pandemia, además de cambios en el abordaje del cuidado y educación de los hijos, conflictos familiares y varios otros aspectos 5,6 . De manera aditiva y sinérgica, todos estos factores tienen consecuencias en la salud de los individuos al alterar sus ritmos circadianos, fenómeno conocido como "cronodisrupción" 7,8 . ...
A pesarde las altas cifras de casos de COVID-19 a nivel mundial, el volumen de individuos afectados por esta pandemia no se limita a las personas infectadas. Notablemente, sus repercusiones se extienden a la población general, tanto en el plano físico como mental. Las medidas de ais-lamiento social, si bien efectivas, obligan a los individuos acambiar drásticamente su rutina diaria al verse sometidos a un estado de confinamiento, una situación de alto estrés. De manera aditiva y sinérgica, todos estos factores tienenconsecuencias en la salud al alterar sus ritmos circadianos, fenómeno conocido como “cronodisrupción”. Esto se asocia con mayor riesgo de diversos trastornos cardiometabólicos. La insulinorresistencia (IR) es un componente fisiopatológico clave en este contexto. La cronodisrupción parecefavorecer el desarrollo de IR a través de alteraciones en su señalización en distintos tejidos periféricos. Además, podría estar vinculada con toxicidad pancreática directa. Esto estaría mediado por disrupciones en la expresión de genes circadianos y alteraciones en la actividad del núcleo supraquiasmático del hipotálamo y la melatonina. El objetivo deesta revisión es describir los posibles mecanismos fisiopatológicos implicados en la cronodisrupción experimentada por los individuos sometidos a periodos de confinamiento y el desarrollo de IR
... Physiological changes [1] , responses to stress [2] , behavioural activities [3] and pathophysiological events are characterised by circadian changes [4] . Removal of the main circadian pacemaker, the suprachiasmatic nucleus [5] , or shifts in the regular light/dark environment [4] diminish circadian amplitude [6] , which can lead to loss of stress predictability [7] in the short term manner. Over the long term, disturbing the circadian oscillations can change system-level set points and may lead to pathological processes [8][9][10] including cancer development [11] . ...
Physiological processes oscillate in time. Circadian oscillations, over approximately 24-h, are very important and among the most studied. To evaluate the presence and significance of 24-h oscillations, physiological time distributed data (TDD) are often set to a cosinor model using a wide range of irregularly updated native apps. If users are familiar with MATLAB, R or other programming languages, users can adjust the parameters of the cosinor model setting based on their needs. Nowadays, many software applications are hosted on remote servers running 24/7. Server-based software applications enable quick analysis of big data sets and run on a wide range of terminal devices using standard web browsers. We created a simple web-based cosinor application, Cosinor.Online. The application code is written in PHP. TDD is handled using a MySQL database and can be copied directly from an Excel file to the webform. Analysis results contain information about setting the 24-h oscillation and a unique ID identifier. The identifier allows users to reopen data and results repeatedly over one month or remove their data from the MySQL database. Our web-based application can be used for a quick and simple inspection of 24-h oscillations of various biological and physiological TDD.
... The physiological mechanisms triggered by chronodisruption are not understood. Experimental studies confirm that long-term disturbances of light conditions reduce the plasticity of the circadian system (Li et al. 2017) and increase unpredictability in the cardiovascular system (Molcan et al. 2014;Molcan and Zeman 2017). These disturbances, in combination with other environmental factors, may lead to an increased cardiovascular risk (Knutsson 2003). ...
Circadian rhythms are an inherent property of physiological processes and can be disturbed by irregular environmental cycles, including artificial light at night (ALAN). Circadian disruption may contribute to many pathologies, such as hypertension, obesity, and type 2 diabetes, but the underlying mechanisms are not understood. Our study investigated the consequences of ALAN on cardiovascular and metabolic parameters in spontaneously hypertensive rats, which represent an animal model of essential hypertension and insulin resistance. Adult males were exposed to a 12 h light − 12 h dark cycle and the ALAN group experienced dim light at night (1–2 lx), either for 2 or 5 weeks. Rats on ALAN showed a loss of light–dark variability for systolic blood pressure, but not for heart rate. Moreover, a gradual increase of systolic blood pressure was recorded over 5 weeks of ALAN. Exposure to ALAN increased plasma insulin and hepatic triglyceride levels. An increased expression of metabolic transcription factors, Pparα and Pparγ, in the epididymal fat and a decreased expression of Glut4 in the heart was found in the ALAN group. Our results demonstrate that low-intensity ALAN can disturb blood pressure control and augment insulin resistance in spontaneously hypertensive rats, and may represent a serious risk factor for cardiometabolic diseases.
This review explores the multifaceted exposures in the workplace that contribute to cardiovascular diseases (CVD), including physical, ergonomics, chemical, biological, psychosocial, and emerging occupational hazards. These well-documented occupational hazards have long been linked to heart disease. Exposures arising from these hazards present significant concerns for worker health and safety. Moreover, heat stress is an emerging and increasingly pervasive threat, exacerbated by climate change, particularly in outdoor, high-exposure industries like agriculture and construction. While the epidemiological links between heat and CVD are well established, there is a critical gap in research on the physiological impacts of heat on workers' cardiovascular health. In particular, migrant workers are especially vulnerable to these occupational hazards, particularly in the absence of targeted, equitable interventions. As global temperatures rise, addressing these occupational exposures is important for protecting the cardiovascular health of the workforce and the expanding field of occupational cardiology.
A network of cellular timers ensures the maintenance of homeostasis by temporal modulation of physiological processes across the day. These so-called circadian clocks are synchronized to geophysical time by external time cues (or zeitgeber s). In modern societies, natural environmental cycles are disrupted by artificial lighting, around-the-clock availability of food or shift work. Such contradictory zeitgeber input promotes chronodisruption, i.e. , the perturbation of internal circadian rhythms, resulting in adverse health outcomes. While this phenomenon is well described, it is still poorly understood at which level of organization perturbed rhythms impact on health and wellbeing. In this review, we discuss different levels of chronodisruption and what is known about their health effects. We summarize the results of disrupted phase coherence between external and internal time vs. misalignment of tissue clocks amongst each other, i.e., internal desynchrony. Last, phase incoherence can also occur at the tissue level itself. Here, alterations in phase coordination can emerge between cellular clocks of the same tissue or between different clock genes within the single cell. A better understanding of the mechanisms of circadian misalignment and its effects on physiology will help to find effective tools to prevent or treat disorders arising from modern-day chronodisruptive environments.
A network of cellular timers ensures the maintenance of homeostasis by temporal modulation of physiological processes across the day. These so-called circadian clocks are synchronized to geophysical time by external time cues (or zeitgeber s). In modern societies, natural environmental cycles are disrupted by artificial lighting, around-the-clock availability of food or shiftwork. Such contradictory zeitgeber input promotes chronodisruption, i.e. , the perturbation of internal circadian rhythms, resulting in adverse health outcomes. While this phenomenon is well described, it is still poorly understood at which level of organization perturbed rhythms impact on health and wellbeing. In this review, we discuss different levels of chronodisruption and what is known about their health effects. We summarize the results of disrupted phase coherence between external and internal time vs. misalignment of tissue clocks amongst each other, i.e., internal desynchrony. Last, phase incoherence can also occur at the tissue level itself. Here, alterations in phase coordination can emerge between cellular clocks of the same tissue or between different clock genes within the single cell. A better understanding of the mechanisms of circadian misalignment and its effects on physiology will help to find effective tools to prevent or treat disorders arising from modern-day chronodisruptive environments.
Cardiovascular (CV) health is often expressed by changes in heart rate and blood pressure, the physiological record of which may be affected by moving, anaesthesia, handling, time of day and many other factors in rodents. Telemetry measurement minimises these modulations and enables more accurate physiological recording of heart rate and blood pressure than non-invasive methods. Measurement of arterial blood pressure by telemetry requires implanting a catheter tip into the artery. Telemetry enables us to sample physiological parameters with a high frequency continuously for several months. By measuring the pressure in the artery using telemetry, we can visualize pressure changes over a heart cycle as the pressure wave. From the pressure wave, we can subtract systolic, diastolic, mean and pulse pressure. From the beat-to-beat interval (pressure wave) and the RR' interval (electrocardiogram), we can derive the heart rate. From beat-to-beat variability, we can evaluate the autonomic nervous system's activity and spontaneous baroreflex sensitivity and their impact on CV activity. On a long-term scale, circadian variability of CV parameters is evident. Circadian variability is the result of the circadian system's activity, which synchronises and organises many activities in the body, such as autonomic and reflex modulation of the CV system and its response to load over the day. In the presented review, we aimed to discuss telemetry devices, their types, implantation, set-up, limitations, short-term and long-term variability of heart rate and blood pressure in CV research. Data collection by telemetry should be, despite some limitations, standard in modern experimental CV research.
Ultradian (∼4 hr) rhythms in locomotor activity that do not depend on the master
circadian pacemaker in the suprachiasmatic nucleus have been observed across mammalian species, however, the underlying mechanisms driving these rhythms are unknown. We show that disruption of the dopamine transporter gene lengthens the period of ultradian locomotor rhythms in mice. Period lengthening also results from chemogenetic activation of midbrain dopamine neurons and psychostimulant treatment, while the antipsychotic haloperidol has the opposite effect. We further reveal that striatal dopamine levels fluctuate in synchrony with ultradian activity cycles and that dopaminergic tone strongly predicts ultradian period. Our data indicate that an arousal regulating, dopaminergic ultradian oscillator (DUO) operates in the mammalian brain, which normally cycles in harmony with the circadian clock, but can desynchronize when dopamine tone is elevated, thereby producing aberrant patterns of arousal which are strikingly similar to perturbed sleep-wake cycles comorbid with psychopathology.
Blood pressure exhibits substantial short- and long-term variability (BPV). We assessed the hypothesis that the complexity of beat-to-beat BPV will be differentially altered in salt-sensitive hypertensive Dahl rats (SS) versus rats protected from salt-induced hypertension (SSBN13) maintained on high-salt versus low-salt diet. Beat-to-beat systolic and diastolic BP series from nine SS and six SSBN13 rats (http://www.physionet.org) were analyzed following 9 weeks on low salt and repeated after 2 weeks on high salt. BP complexity was quantified by detrended fluctuation analysis (DFA), short- and long-range scaling exponents (αS and αL), sample entropy (SampEn), and traditional standard deviation (SD) and coefficient of variation (CV(%)). Mean systolic and diastolic BP increased on high-salt diet (P < 0.01) particularly for SS rats. SD and CV(%) were similar across groups irrespective of diet. Salt-sensitive and -protected rats exhibited similar complexity indices on low-salt diet. On high salt, (1) SS rats showed increased scaling exponents or smoother, systolic (P = 0.007 [αL]) and diastolic (P = 0.008 [αL]) BP series; (2) salt-protected rats showed lower SampEn (less complex) systolic and diastolic BP (P = 0.046); and (3) compared to protected SSBN13 rats, SS showed higher αL for systolic (P = 0.01) and diastolic (P = 0.005) BP Hypertensive SS rats are more susceptible to high salt with a greater rise in mean BP and reduced complexity. Comparable mean pressures in sensitive and protective rats when on low-salt diet coupled with similar BPV dynamics suggest a protective role of low-salt intake in hypertensive rats. This effect likely reflects better coupling of biologic oscillators.
One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations—similar fluctuation structure at different time scales—that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)—a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)—the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The differential impacts of food restriction on fractal activity control in intact and DMH-lesioned animals suggest that the DMH plays a crucial role in integrating these different time cues to the circadian network for multiscale regulation of motor activity.
Significance
Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease, even after controlling for traditional risk factors. Shift workers frequently undergo circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles). This misalignment has been proposed to explain, in part, why shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. However, the impact of circadian misalignment per se on 24-h blood pressure and inflammatory markers is poorly understood. We show—under highly controlled laboratory conditions—that short-term circadian misalignment increases 24-h blood pressure and inflammatory markers in healthy adults. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.
Background and objectives:
Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis.
Materials and methods:
Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated.
Results:
A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617-0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007-0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033-0.362, P = 0.0003).
Conclusion:
Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD.
Objectives:
Clinical and experimental research studies have demonstrated that the emotional experience of anxiety impairs heart rate variability (HRV) in humans. The present study investigated whether changes in state anxiety (SA) can also modulate nonlinear dynamics of heart rate.
Methods:
A group of 96 students volunteered to participate in the study. For each student, two 5-minute recordings of beat intervals (RR) were performed: one during a rest period and one just before a university examination, which was assumed to be a real-life stressor. Nonlinear analysis of HRV was performed. The Spielberger's State-Trait Anxiety Inventory was used to assess the level of SA.
Results:
Before adjusting for heart rate, a Wilcoxon matched pairs test showed significant decreases in Poincaré plot measures, entropy, largest Lyapunov exponent (LLE), and pointwise correlation dimension (PD2), and an increase in the short-term fractal-like scaling exponent of detrended fluctuation analysis (α1) during the exam session, compared with the rest period. A Pearson analysis indicated significant negative correlations between the dynamics of SA and Poincaré plot axes ratio (SD1/SD2), and between changes in SA and changes in entropy measures. A strong negative correlation was found between the dynamics of SA and LLE. A significant positive correlation was found between the dynamics of SA and α1. The decreases in Poincaré plot measures (SD1, complex correlation measure), entropy measures, and LLE were still significant after adjusting for heart rate. Corrected α1 was increased during the exam session. As before, the dynamics of adjusted LLE was significantly correlated with the dynamics of SA.
Conclusions:
The qualitative increase in SA during academic examination was related to the decrease in the complexity and size of the Poincaré plot through a reduction of both the interbeat interval and its variation.
Effects of phase delay shifts (PDS) of light in combination with moderately increased salt intake (SL) (2%) or time restriction of food (FR) during the light-time (passive phase) on heart rate (HR), blood pressure (BP) and locomotor activity (LA) in radiotelemetry-measured rats were evaluated. PDS decreased amplitude and spectral power of circadian oscillations of HR, BP and LA. Moderately increased SL did not interfere with the circadian rhythmicity of HR, BP or LA. A prominent decrease in amplitude and spectral power of circadian oscillations was observed if food was available during the lighttime. Combination of PDS with FR split cardiovascular and behavioural parameters. In conclusion, food availability during the light-time in combination with PDS decreased amplitude and spectral power of circadian oscillations of BP, HR and LA more than PDS only. Different response of cardiovascular and behavioural parameters to photic and non-photic stimuli can have consequences for shift workers.
Both heart rate (HR) and brain functioning involve the integrated output of a multitude of regulatory mechanisms, that are not quantified adequately by linear approximations such as means and standard deviations. It was therefore considered whether non-linear measures of HR complexity are more strongly associated with cognition and mood. Whilst resting, the inter-beat (R-R) time series of twenty-one males and twenty-four females were measured for five minutes. The data were summarised using time, frequency and nonlinear complexity measures. Attention, memory, reaction times, mood and cortisol levels were assessed. Nonlinear HR indices captured additional information, enabling a greater percentage of the variance in behaviour to be explained. On occasions non-linear indices were related to aspects for behaviour, for example focused attention and cortisol production, when time or frequency indices were not. These effects were sexually dimorphic with HR complexity being more strongly associated with the behaviour of females. It was concluded that nonlinear rather than linear methods of summarizing the HR times series offers a novel way of relating brain functioning and behaviour. It should be considered whether non-linear measures of HR complexity can be used as a biomarker of the integrated functioning of the brain.
The aims of this subanalysis of the COLM trial [NCT00454662] were to compare visit-to-visit variability (VVV) of blood pressure (BP) between age groups and between two treatment combinations, that is, the angiotensin II receptor blocker, olmesartan combined with a calcium channel blocker (CCB), or a diuretic and to investigate the effect of VVV of BP on cardiovascular events in elderly hypertensive patients.
Hypertensive patients ages 65-84 years with a history of and/or risk factors for cardiovascular disease were randomized to receive treatment with olmesartan along with either a CCB or a diuretic for at least 3 years. This subanalysis comprised 4876 patients who had their office BP measured at least three occasions (median nine occasions) during the follow-up period. VVV of BP was defined by several metrics including the within-individual standard deviation of every visit during the follow-up period.
VVV of SBP was larger in the very elderly group (75-84 years) than in the elderly group (65-74 years). VVV of SBP was smaller in the olmesartan along with CCB group than in the olmesartan along with diuretic group, especially in very elderly patients and also isolated systolic hypertensive patients. The incidence rate of primary endpoint increased along with an increment in the SD of SBP in all of the age and treatment groups.
VVV of SBP may mediate the preferable effect of combination of angiotensin II receptor blocker along with CCB on cardiovascular events in the very elderly and also isolated systolic hypertensive patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.
Systolic hypertension is associated with cognitive decline in the elderly. Altered blood pressure (BP) variability is a possible mechanism of reduced cognitive performance in elderly hypertensives. We hypothesized that altered beat-to-beat systolic BP variability is associated with reduced global cognitive performance in elderly hypertensive subjects. In exploratory analyses, we also studied the correlation between diverse discrete cognitive domains and indices of systolic BP and heart rate variability. Disproving our initial hypothesis, we have shown that hypertension and low education, but not indices of systolic BP and heart rate variability, were independent predictors of lower global cognitive performance. However, exploratory analyses showed that the systolic BP variability in semi-upright position was an independent predictor of matrix reasoning (B=0.08±.03, P-value=0.005), whereas heart rate variability in semi-upright position was an independent predictor of the executive function score (B=-6.36±2.55, P-value=0.02). We conclude that myogenic vascular and sympathetic modulation of systolic BP do not contribute to reduced global cognitive performance in treated hypertensive subjects. Nevertheless, our results suggest that both systolic BP and heart rate variability might be associated with modulation of frontal lobe cognitive domains, such as executive function and matrix reasoning.Journal of Human Hypertension advance online publication, 18 December 2014; doi:10.1038/jhh.2014.119.
Background: Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis.
Method: Studies comparing resting-state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis.
Results: Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterized by lower HRV [high frequency (HF): Hedges’ g = −0.29. 95% CI: −0.41 to −0.17, p < 0.001; time domain: Hedges’ g = −0.45, 95% CI: −0.57 to −0.33, p < 0.001] than controls. Panic disorder (n = 447), post-traumatic stress disorder (n = 192), generalized anxiety disorder (n = 68), and social anxiety disorder (n = 90), but not obsessive–compulsive disorder (n = 40), displayed reductions in HF HRV relative to controls (all ps < 0.001).
Conclusion: Anxiety disorders are associated with reduced HRV, findings associated with a small-to-moderate effect size. Findings have important implications for future physical health and well-being of patients, highlighting a need for comprehensive cardiovascular risk reduction.
Background
We evaluated the effects of the PCM on the fractal analysis of the HRV in healthy women
Method
We evaluated healthy women between 18 and 30 years old. HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains as well as short and long-term fractal exponents (alpha-1 and alpha-2) of the detrended fluctuation analysis (DFA). HRV was recorded at rest for ten minutes at seated rest and then the women quickly stood up from a seated position in up to three seconds and remained standing for 15 minutes. HRV was recorded at the following time: rest, 0–5 min, 5–10 min and 10–15 min during standing.
Results
We observed decrease (p < 0.05) in the time-domain indices of HRV between seated and 10–15 minutes after the volunteer stood up. The LF (ms2) and HF (ms2) indices were also reduced (p < 0.05) at 10–15 minutes after the volunteer stood up compared to seated while the LF (nu) was increased at 5–10 min and 10–15 min (p < 0.05). The short-term alpha-1 exponent was increased (p < 0.05) at all moments investigated compared to seated. Increase in the properties of short-term fractal correlations of heart rate dynamics accompanied by a decrease in the parasympathetic modulation and global HRV was observed in response to the postural change maneuver.
Conclusion
We suggest that fractal analysis of HRV is more sensitive than frequency and time-domain analysis of HRV during the postural change maneuver.
Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronised activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions.
Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation.
Cardiovascular parameters, such as blood pressure and heart rate, exhibit both circadian and ultradian rhythms which are important for the adequate functioning of the system. For a better understanding of possible negative effects of chronodisruption on the cardiovascular system we studied circadian and ultradian rhythms of blood pressure and heart rate in rats exposed to repeated 8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks, with three shifts per week. Spectral power as a function of frequency for both circadian and harmonic ultradian rhythms was expressed as the circadian-ultradian power ratio. The circadian rhythms of blood pressure, heart rate and locomotor activity were recorded during the control light:dark (LD) regimen with higher values during the D in comparison with the L. Phase advance shifts resulted in a diminished circadian-ultradian power ratio for blood pressure, heart rate and locomotor activity indicating suppressed circadian control of these traits greater in heart rate than blood pressure. In conclusion, rats kept under irregular LD conditions have suppressed circadian control of heart rate, blood pressure and locomotor activity and rely more on an acute response to the LD regime. Their ability to anticipate regular loads can be weakened and in this way chronodisruption can contribute to the pathogenesis of cardiovascular diseases.
Circadian variation in cardiac autonomic nervous system activity and behavior during the day shifts of shift workers has not hitherto been clarified. This study examined diurnal 24-h variation in heart rate variability (HRV), sleep-wake cycle, physical activity, and food intake during the day shift in rotating shift workers. The subjects were female nurses and caregivers working at a health care facility (14 day workers and 13 rotating shift workers). Each subject was asked to undergo 24-h electrocardiograph and step count recordings. Coarse graining spectral analysis was used for approximately 10-min segments of HRV (600 beats) to derive the total power (TOT: >0.04 Hz), integrated power in the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: >0.15 Hz) ranges, the ratio of HF power to TOT (HF nu), and the ratio of LF power to HF power (LF/HF). Double cosinor analysis was used to obtain 24-h and 12-h period variations in variables of HRV and physical activity. While no difference was found in the acrophases of either period for step counts or in the 12-h period of HRV variables between the groups, the acrophases of the 24-h period for HRV variables were delayed by 1.3 to 5.5 h in rotating shift workers, and their differences in HF power, HF nu, and LF/HF reached a significant level (p < 0.05). On the days of the experiment, retiring time, waking up time, total time in bed, sleep efficiency, and mealtimes and energy intake for each diet did not differ between the groups. These results suggest that there is a possibility of an abnormal phase angle between circadian variation in cardiac autonomic nervous system activity and the sleep-wake cycle during the day shift in shift workers.
The mammalian central circadian pacemaker (the suprachiasmatic nucleus, SCN) contains thousands of neurons that are coupled through a complex network of interactions. In addition to the established role of the SCN in generating rhythms of ,24 hours in many physiological functions, the SCN was recently shown to be necessary for normal self-similar/fractal organization of motor activity and heart rate over a wide range of time scales—from minutes to 24 hours. To test whether the neural network within the SCN is sufficient to generate such fractal patterns, we studied multi-unit neural activity of in vivo and in vitro SCNs in rodents. In vivo SCN-neural activity exhibited fractal patterns that are virtually identical in mice and rats and are similar to those in motor activity at time scales from minutes up to 10 hours. In addition, these patterns remained unchanged when the main afferent signal to the SCN, namely light, was removed. However, the fractal patterns of SCN-neural activity are not autonomous within the SCN as these patterns completely broke down in the isolated in vitro SCN despite persistence of circadian rhythmicity. Thus, SCN-neural activity is fractal in the intact organism and these fractal patterns require network interactions between the SCN and extra-SCN nodes. Such a fractal control network could underlie the fractal regulation observed in many physiological functions that involve the SCN, including motor control and heart rate regulation.
In this work we characterized the non-linear complexity of Heart Rate Variability (HRV) in short time series. The complexity of HRV signal was evaluated during emotional visual elicitation by using Dominant Lyapunov Exponents (DLEs) and Approximate Entropy (ApEn). We adopted a simplified model of emotion derived from the Circumplex Model of Affects (CMAs), in which emotional mechanisms are conceptualized in two dimensions by the terms of valence and arousal. Following CMA model, a set of standardized visual stimuli in terms of arousal and valence gathered from the International Affective Picture System (IAPS) was administered to a group of 35 healthy volunteers. Experimental session consisted of eight sessions alternating neutral images with high arousal content images. Several works can be found in the literature showing a chaotic dynamics of HRV during rest or relax conditions. The outcomes of this work showed a clear switching mechanism between regular and chaotic dynamics when switching from neutral to arousal elicitation. Accordingly, the mean ApEn decreased with statistical significance during arousal elicitation and the DLE became negative. Results showed a clear distinction between the neutral and the arousal elicitation and could be profitably exploited to improve the accuracy of emotion recognition systems based on HRV time series analysis.
There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction.
To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal).
A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use.
HRV was calculated from electrocardiography under a standardized short-term resting state condition.
HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size.
Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.
This study investigates the variations of Heart Rate Variability (HRV) due to a real-life stressor and proposes a classifier based on nonlinear features of HRV for automatic stress detection.
42 students volunteered to participate to the study about HRV and stress. For each student, two recordings were performed: one during an on-going university examination, assumed as a real-life stressor, and one after holidays. Nonlinear analysis of HRV was performed by using Poincaré Plot, Approximate Entropy, Correlation dimension, Detrended Fluctuation Analysis, Recurrence Plot. For statistical comparison, we adopted the Wilcoxon Signed Rank test and for development of a classifier we adopted the Linear Discriminant Analysis (LDA).
Almost all HRV features measuring heart rate complexity were significantly decreased in the stress session. LDA generated a simple classifier based on the two Poincaré Plot parameters and Approximate Entropy, which enables stress detection with a total classification accuracy, a sensitivity and a specificity rate of 90%, 86%, and 95% respectively.
The results of the current study suggest that nonlinear HRV analysis using short term ECG recording could be effective in automatically detecting real-life stress condition, such as a university examination.
In spontaneously hypertensive rats (SHR), chronic infusion of clonidine failed to decrease blood pressure and blood pressure variability. We used nonlinear methods to get a deeper insight on the effects of clonidine on blood pressure dynamics. For 24 h and 4 wk, clonidine (0.1 mg . kg-1 . day-1 sc) was infused by minipumps in the conscious SHRs, and, for comparison, a vehicle was infused in SHRs and in Wistar-Kyoto rats. Blood pressure was recorded for 30 min before and after treatments. We used the Lyapunov exponent, approximated by the inverse of the lmax index derived from the recurrence plot method, to characterize nonlinear dynamics. Before treatment, lmax index of blood pressure was lower (P < 0.01) in the SHRs than in the Wistar-Kyoto rats. Clonidine significantly increased lmax (P < 0.01) to the level observed in normotensive rats, at 24 h and up to 4 wk after infusion. We conclude that clonidine has a significant chronic effect on blood pressure dynamics, as evidenced by nonlinear methods. Our study also suggests that the mechanisms governing blood pressure variations are nonlinear.
Circadian clocks are endogenous oscillators driving daily rhythms in physiology and behavior. Synchronization of these timers to environmental light-dark cycles ('entrainment') is crucial for an organism's fitness. Little is known about which oscillator qualities determine entrainment, i.e., entrainment range, phase and amplitude. In a systematic theoretical and experimental study, we uncovered these qualities for circadian oscillators in the suprachiasmatic nucleus (SCN-the master clock in mammals) and the lung (a peripheral clock): (i) the ratio between stimulus (zeitgeber) strength and oscillator amplitude and (ii) the rigidity of the oscillatory system (relaxation rate upon perturbation) determine entrainment properties. Coupling among oscillators affects both qualities resulting in increased amplitude and rigidity. These principles explain our experimental findings that lung clocks entrain to extreme zeitgeber cycles, whereas SCN clocks do not. We confirmed our theoretical predictions by showing that pharmacological inhibition of coupling in the SCN leads to larger ranges of entrainment. These differences between master and the peripheral clocks suggest that coupling-induced rigidity in the SCN filters environmental noise to create a robust circadian system. Molecular Systems Biology 6: 438; published online 30 November 2010; doi:10.1038/msb.2010.92
Heart rate variability (HRV) markers have been widely used to characterize the autonomous regulation state of the heart from 24-h Holter monitoring, but long-term evolution of HRV indexes is mostly unknown. A dataset of 7-day Holter recordings of 22 patients with congestive heart failure was studied. A rhythmometric procedure was designed to characterize the infradian, circadian, and ultradian components for each patient, as well as circadian and ultradian fluctuations. Furthermore, a bootstrap test yielded automatically the rhythmometric model for each patient. We analyzed the temporal evolution of relevant time-domain (AVNN, SDNN, and NN50), frequency-domain (LF, HF, HFn, and LF/HF), and nonlinear (alpha(1) and SampEn) HRV indexes. Circadian components were the most significant for all HRV indexes, but the infradian ones were also strongly present in NN50, HFn, LF/HF, alpha(1), and SampEn indexes. Among ultradian components that one corresponding to 12 h, was the most relevant. Long-term monitoring of HRV conveys new potentially relevant rhythmometric information, which can be analyzed by using the proposed automatic procedure.
Oscillations of heart rate and blood pressure are related to the activity of the underlying control mechanism. They have been investigated mostly with linear methods in the time and frequency domains. Also, in recent years, many different nonlinear analysis methods have been applied for the evaluation of cardiovascular variability. This review presents the most commonly used nonlinear methods. Physiological understanding is obtained from various results from small animals.
We describe a non-profit software package for the computerized analysis of ambulatory blood pressure monitoring (ABPM) recordings, in order to make it available to researchers in cardiovascular physiology, pharmacology and medicine. The first program, ABPM-FIT, can load data from several ABPM devices directly as they are stored on disk, making complicated data conversion steps unnecessary. The program performs conventional linear analyses of ABPM data automatically by calculation of mean, SD, load (the percentage of data above a chosen limit), and highest and lowest readings in user-defisned day and night periods. In addition, the area under the parameter-time curve (AUC) and the weighted mean (AUC/time) is calculated for all parameters monitored. In a second step, ABPM-FIT performs a rhythm analysis by fitting partial Fourier series to the data. Only those hormonics are included which significantly reduce the residual variance of the fit. The parameters of these functions (mesor, amplitudes, acrophases), values derived from the composed curves (maximum and minimum, AUC) and their slopes (e.g. maximal increase and decrease) are calculated automatically and, if desired, saved on disk. The second program, CV-SORT, loads groups of result files saved by ABPM-FIT, allows the extraction of parameters of interest for further analyses and creates spreadsheets containing the selected values from groups of patients. In addition, CV-SORT performs simple statistics, and calculates group mean circadian blood pressure and heart rate profiles from individual Fourier curves, with SD, confidence intervals or percentiles. The features of both programs are shown in exemplary analyses of ABPM recordings.
There is evidence that physiological signals under healthy conditions may have a fractal temporal structure. Here we investigate the possibility that time series generated by certain physiological control systems may be members of a special class of complex processes, termed multifractal, which require a large number of exponents to characterize their scaling properties. We report on evidence for multifractality in a biological dynamical system, the healthy human heartbeat, and show that the multifractal character and nonlinear properties of the healthy heart rate are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure.
Entropy, as it relates to dynamical systems, is the rate of information production. Methods for estimation of the entropy of a system represented by a time series are not, however, well suited to analysis of the short and noisy data sets encountered in cardiovascular and other biological studies. Pincus introduced approximate entropy (ApEn), a set of measures of system complexity closely related to entropy, which is easily applied to clinical cardiovascular and other time series. ApEn statistics, however, lead to inconsistent results. We have developed a new and related complexity measure, sample entropy (SampEn), and have compared ApEn and SampEn by using them to analyze sets of random numbers with known probabilistic character. We have also evaluated cross-ApEn and cross-SampEn, which use cardiovascular data sets to measure the similarity of two distinct time series. SampEn agreed with theory much more closely than ApEn over a broad range of conditions. The improved accuracy of SampEn statistics should make them useful in the study of experimental clinical cardiovascular and other biological time series.
The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state [Physiol. Rev. 9, 399-431 (1929)]. However, recent studies [Phys. Rev. Lett. 70, 1343-1346 (1993); Fractals in Biology and Medicine (Birkhauser-Verlag, Basel, 1994), pp. 55-65] reveal that under normal conditions, beat-to-beat fluctuations in heart rate display the kind of long-range correlations typically exhibited by dynamical systems far from equilibrium [Phys. Rev. Lett. 59, 381-384 (1987)]. In contrast, heart rate time series from patients with severe congestive heart failure show a breakdown of this long-range correlation behavior. We describe a new method--detrended fluctuation analysis (DFA)--for quantifying this correlation property in non-stationary physiological time series. Application of this technique shows evidence for a crossover phenomenon associated with a change in short and long-range scaling exponents. This method may be of use in distinguishing healthy from pathologic data sets based on differences in these scaling properties.
Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g. spectral analysis). However, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control, namely rats with heart failure (HF), spontaneously hypertensive rats (SHRs) and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared to controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency and information domains.
Increased blood pressure variability has been shown to be associated with cardiovascular morbidity and mortality. Recently we reported that continuous infusion of angiotensin II not only elevated blood pressure level, but also increased blood pressure variability in a manner assumed to be independent of blood pressure elevation in rats. In the present study, the effects of the angiotensin type I receptor blocker losartan and the calcium channel blocker azelnidipine on angiotensin II-induced blood pressure variability were examined and compared with that of the vasodilator hydralazine in rats. Nine-week-old male Wistar rats were subcutaneously infused with 240 pmol/kg/min angiotensin II for two weeks without or with oral administration of losartan, azelnidipine, or hydralazine. Blood pressure variability was evaluated using a coefficient of variation of blood pressure recorded every 15 min under an unrestrained condition via an abdominal aortic catheter by a radiotelemetry system. Treatment with losartan suppressed both blood pressure elevation and augmentation of systolic blood pressure variability in rats infused with angiotensin II at 7 and 14 days. Azelnidipine also inhibited angiotensin II-induced blood pressure elevation and augmentation of blood pressure variability; meanwhile, hydralazine attenuated the pressor effect of angiotensin II, but had no effect on blood pressure variability. In conclusion, angiotensin II augmented blood pressure variability in an angiotensin type 1 receptor-dependent manner, and azelnidipine suppressed angiotensin II-induced augmentation of blood pressure variability, an effect mediated by the mechanism independent of the blood pressure-lowering action.
Atrial fibrillation is the most commonly confronted cardiac arrhythmia in humans. This paper is written to use sample entropy and percentage of atrial fibrillation as a measure of regularity to measure AF. To assume the percentage of AF, 25 long-term ECG recordings of human subjects with atrial fibrillation containing a total of 299 AF episodes were processed. The mean and SD of percentage breaking point in all the subjects from the MIT-BIH Atrial Fibrillation database was 0.606±0.086, and its sample entropy is 0.352±0.151. The mean and SD for sample entropy at 100% AF is 1.067±0.452. This data is used to predict the percentage of AF at a given sample entropy value. Our study concludes that the early detection of AF can be initiated by the AF already happened for 60%.
Disturbances in regular circadian oscillations can have negative effects on cardiovascular function, but epidemiological data are inconclusive and new data from animal experiments elucidating critical biological mechanisms are needed. To evaluate the consequences of chronic phase shifts of the light/dark (LD) cycle on hormonal and cardiovascular rhythms, two experiments were performed. In Experiment 1, male rats were exposed to either a regular 12:12 LD cycle (CONT) or rotating 8-h phase-delay shifts of LD every second day (SHIFT) for 10 weeks. During this period, blood pressure (BP) was monitored weekly, and daily rhythms of melatonin, corticosterone, leptin and testosterone were evaluated at the end of the experiment. In Experiment 2, female rats were exposed to the identical shifted LD schedule for 12 weeks, and daily rhythms of BP, heart rate (HR) and locomotor activity were recorded using telemetry. Preserved melatonin rhythms were found in the pineal gland, plasma, heart and kidney of SHIFT rats with damped amplitude in the plasma and heart, suggesting that the central oscillator can adapt to chronic phase-delay shifts. In contrast, daily rhythms of corticosterone, testosterone and leptin were eliminated in SHIFT rats. Exposure to phase shifts did not lead to increased body weight and elevated BP. However, a shifted LD schedule substantially decreased the amplitude and suppressed the circadian power of the daily rhythms of BP and HR, implying weakened circadian control of physiological and behavioural processes. The results demonstrate that endocrine and cardiovascular rhythms can differentially adapt to chronic phase-delay shifts, promoting internal desynchronization between central and peripheral oscillators, which in combination with other negative environmental stimuli may result in negative health effects.
Decreased oxygenation during pregnancy and early periods of ontogeny can affect normal body development and result in diseases in adulthood. The aim of this study was to use the model of prenatal intermittent hypoxia (PIH) and evaluate the effects of short-term hypoxia at the end of gestation on blood pressure (BP) control in adulthood. Wistar rats were exposed daily to PIH for 4 h during gestational day 19 and 20. In adult male rats, heart rate (HR), systolic BP and pulse pressure (PP) were acquired by radiotelemetry during 1 week. On the basis of HR variability and BP variability, sympathovagal balance (LF/HF) and spontaneous baroreflex sensitivity (sBRS) were evaluated. Systolic BP and PP were significantly elevated in PIH rats in comparison with control rats during the light and dark phase of the day, while LF/HF increased only during the light phase of the day. In contrast, sBRS tended to decrease only during the dark phase in PIH rats. In all measured and calculated parameters, significant circadian rhythms were present and were not affected by PIH. In conclusion, our data suggest that short intermittent hypoxia at the end of gestation can increase BP and PP via significant changes in LF/HF, which occur especially during the passive phase of the day. Results suggest that minor changes in the autonomous nervous system activity induced by environmental conditions during the perinatal period may contribute to development of hypertension in adulthood.Hypertension Research advance online publication, 25 February 2016; doi:10.1038/hr.2016.21.
Autonomic dysfunction is implicated in prehypertension, and previous studies have suggested that therapies that improve modulation of sympathovagal balance, such as biofeedback and slow abdominal breathing, are effective in patients with prehypertension at rest. However, considering that psychophysiological stressors may be associated with greater cardiovascular risk in prehypertensives, it is important to investigate whether heart rate variability biofeedback (HRV-BF) results in equivalent effects on autonomic cardiovascular responses control during stressful conditions in prehypertensives. A total of 32 college students with prehypertension were enrolled and randomly assigned to HRV-BF (n=12), slow abdominal breathing (SAB, n=10) or no treatment (control, n=10) groups. Then, a training experiment consisting of 15 sessions was employed to compare the effect of each intervention on the following cardiovascular response indicators before and after intervention: heart rate (HR); heart rate variability (HRV) components; blood volume pulse amplitude (BVPamp); galvanic skin response; respiration rate (RSP); and blood pressure. In addition, the cold pressor test and the mental arithmetic challenge test were also performed over two successive days before and after the invention as well as after 3 months of follow-up. A significant decrease in HR and RSP and a significant increase in BVPamp were observed after the HRV-BF intervention (P<0.001). For the HRV analysis, HRV-BF significantly reduced the ratio of low-frequency power to high-frequency power (the LF/HF ratio, P<0.001) and increased the normalized high-frequency power (HFnm) (P<0.001) during the stress tests, and an added benefit over SAB by improving HRV was also observed. In the 3-month follow-up study, similar effects on RSP, BVPamp, LF/HF and HFnm were observed in the HRV-BF group compared with the SAB group. HRV-BF training contributes to the beneficial effect of reducing the stress-related cardiovascular response in prehypertensives by improving autonomic sympathovagal modulation.Journal of Human Hypertension advance online publication, 30 April 2015; doi:10.1038/jhh.2015.27.
Chronic stress detection is an important factor in predicting and reducing the risk of cardiovascular disease. This work is a pilot study with a focus on developing a method for detecting short-term psychophysiological changes through heart rate variability (HRV) features. The purpose of this pilot study is to establish and to gain insight on a set of features that could be used to detect psychophysiological changes that occur during chronic stress. This study elicited four different types of arousal by images, sounds, mental tasks and rest, and classified them using linear and non-linear HRV features from electrocardiograms (ECG) acquired by the wireless wearable ePatch® recorder. The highest recognition rates were acquired for the neutral stage (90%), the acute stress stage (80%) and the baseline stage (80%) by sample entropy, detrended fluctuation analysis and normalized high frequency features. Standardizing non-linear HRV features for each subject was found to be an important factor for the improvement of the classification results.
Background
Blood pressure (BP) is monitored and managed to prevent cardiovascular complications of hypertension, but BP variability (BPV) has not been sufficiently studied. This analysis assessed whether patients receiving amlodipine versus other antihypertensive agents had lower BPV after ≥12 weeks of treatment.
Methods
Studies were included if individual subject data were available, had ≥1 active comparator, and treatment duration was ≥12 weeks. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) of systolic BP across visits from 12 weeks. Individual trial and meta-analyses were performed for SD- and CV-based methodology.
Results
Five studies (47,558 BPV-evaluable patients) were included. Patient characteristics were largely consistent across the studies, but BP measurements varied from ∼4 months to ∼6 years. BPV with amlodipine was significantly (P < .0001) lower versus atenolol and lisinopril; significantly (P < .0001) lower than enalapril in one study and numerically, but not significantly lower in another; and similar to chlorthalidone and losartan. Meta-analysis revealed a treatment difference (standard error) for amlodipine versus all active comparators of –1.23 (0.46, P = .008) mm Hg using SD and –0.86 (0.31, P = .005) using CV.
Conclusions
These findings suggest that amlodipine is effective for minimizing BPV. Future studies need to confirm a causal link between BPV and cerebrovascular/cardiovascular outcomes. Word count = 211
Background/Purpose
Reduced heart rate variability (HRV) has been shown to be associated with a risk of cardiovascular disease. The combined influence of shift work and menstrual cycle on HRV in nurses has not been studied. The aim of this study was to examine the effects of the menstrual cycle within shift patterns on HRV in nurses, using a within-subjects design and a multivariable analysis to control covariates.
Methods
Twelve healthy, young, female shift nurses volunteered to have repeat measures of female sex hormones, 24-hour physical activity, and HRV at three points, during their menses, follicular, and luteal phases.
Results
Normal cyclic variations in endogenous sex hormones levels were shown; however, no significant correlations were found between estrogen levels and HRV variables. Results demonstrated that the high frequency (HF) was lower in the follicular phase than in the luteal phases; however, the low frequency (LF) or LF to HF ratio (LF/HF) was significantly higher in the follicular phase than in the luteal phase during sleeping periods after night or day work.
Conclusion
The endogenous sex hormones levels were shown normal cyclic variation. Under the effects of shift work, the diminished parasympathetic activity and the increased sympathetic activity were shown in the follicular phase compared with the luteal phase. This result may serve as a reference to explain why shift workers have high risk of cardiovascular disease.
A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent α) and power-law scaling (exponent β) were studied in 159 patients with depressed LV function (ejection fraction
Monocrotaline (MCT) is commonly used to experimentally induce pulmonary hypertension (PH), which might lead to chronic heart failure. In this study, linear and non-linear heart rate (HR) dynamics were weekly assessed in MCT-treated and non-treated Wistar rats. The HR of 10 adult Wistar rats injected with MCT (MCT group) and of 10 similar rats injected with vehicle (non-MCT group), anesthetized with Ketamine, was weekly recorded during 4 weeks. The first four segments of 1-min length of each HR recording were analysed using linear, time and frequency domains, and approximate (ApEn) and sample (SampEn) entropy indices, considering recently proposed values for the threshold parameter of ApEn and SampEn. Statistical analysis was performed using 95% confidence intervals and statistical tests. Along the study period, an overall weekly maintenance of HR indices, or a decrease, namely in weeks 1-2, was manifest, in the MCT group, except for LF and LF/HF, in week 1, denoting a short-term increase in sympathetic activity without any other changes. On the other hand, a maintenance of HR indices, or an increase, namely on week 4, was observed in the non-MCT group, except for LF/HF, denoting a long-term increase of the overall activity of HR control systems, with a parasympathetic like dominance. Studies on long-term HR dynamics should be performed in very carefully controlled experimental settings, as significant weekly changes may occur, both among anesthetized MCT-treated and non-treated rats.
Approximate entropy (ApEn), a recently developed mathematical formula quantifying regularity, was applied to fetal heart rate (FHR) data. Three groups were analyzed: 1) 19 women had normal labors (uncomplicated course of labor, vaginal delivery, no unusual FHR tracings, and 1- and 5-minute Apgar scores of at least 7 and 9, respectively; 2) 15 women had presumed fetal distress (severe cord or late decelerations, bradycardia, or tachycardia; delivery by cesarean with both arterial and venous cord pH above 7.20); and 3) 20 women had acidotic fetuses (both venous and arterial cord pH less than 7.20). Hourly mean (+/- SD) ApEn values for the three groups were: acidotic fetuses, 0.924 +/- 0.235, 102 hours; normal fetuses, 1.051 +/- 0.145, 97 hours; and nonacidotic "distressed" fetuses, 1.043 +/- 0.147, 74 hours. The ApEn values for nonacidotic, presumed distressed fetuses were not significantly different from those of normal fetuses (P greater than .75). Acidotic fetuses had many more instances of ApEn hourly values less than 0.8 (28%, 29 of 102) than did the normal and the nonacidotic, presumed distressed fetuses combined (5%, nine of 171). The probability that ApEn was less than 0.8 was larger for acidotic fetuses than for the other groups (P less than .00003), supporting the hypothesis that extremely regular FHR patterns imply a greater likelihood of acidosis. Significant hourly deviations in ApEn generally corresponded to drug administration or to physiologic changes such as cord compression and its relief. Thus ApEn, a major departure from variability statistics, appears to be able to detect subtle and possibly important differences in heart rate that are not visually apparent.
Accurate continuous chronic measurements of blood pressure from conscious laboratory rats are critical to many experimental protocols but have been difficult or impossible to acquire. A system consisting of an implantable radio-telemetry device, receiver, and computer-based data acquisition system that allows such measurements to be easily obtained has been developed. This system is capable of monitoring and recording arterial pressure (waveform, systolic, diastolic, and mean), heart rate, and activity from rats weighing greater than 175 gm for periods in excess of 6 months. Chronic patency has been achieved through a patented design which includes an antithrombogenic film and a gel membrane located at the catheter tip. Validation of telemetered measurements via carotid catheter has demonstrated the accuracy to be better than +/- 5 mmHg in 85% (N = 20) tested at 3 weeks post implantation, 86% (N = 15) tested at 8 weeks, and 78% (N = 9) at 12 weeks. Incidence of loss of patency was 2.3% (N = 44). This system has a demonstrated ability to obtain accurate continuous chronic measurements of arterial pressure free of the stressors associated with conventional systems.
We investigated the fluctuations which underly the spontaneous variability of blood pressure and heart rate in conscious rats. Intrafemoral blood pressure was computed to generate evenly spaced signals (systolic, diastolic, mean blood pressure, heart rate) at 200 ms intervals. This equidistant sampling allowed a direct spectral analysis using a Fast Fourier Transform algorithm. Systolic blood pressure and heart rate exhibited low-frequency oscillations (Mayer waves, 20-605 mHz) and a high- frequency oscillation related to respiration (1855 mHz). The respiratory fluctuations in heart rate were almost abolished by vagal blockade (atropine). Heart rate fluctuations in the low-frequency regime were diminished by vagal blockade or cardiac sympathetic blockade (atenolol). The respiratory frequency fluctuations in systolic blood pressure were markedly increased by alpha-sympathetic blockade (prazosin). In contrast, the low-frequency oscillations in systolic blood pressure were reduced by alpha-sympathetic blockade. These data indicate that in conscious rats: (1) the heart rate oscillation with respiration is vagally mediated; (2) the heart rate fluctuation in the low-frequency range is jointly mediated by beta-sympathetic and parasympathetic activities; (3) the respiratory oscillation in systolic blood pressure depends on fluctuations in cardiac output and is normally counteracted by the sympathetic tone; (4) the low-frequency oscillations in systolic blood pressure reflect the sympathetic activity to the resistance vessels.
Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.
Dynamic analysis techniques may uncover abnormalities in heart rate (HR) behavior that are not easily detectable with conventional statistical measures. However, the applicability of these new methods for detecting possible abnormalities in HR behavior in various cardiovascular disorders is not well established. Conventional measures of HR variability were compared with short-term (< or = 11 beats, alpha1) and long-term (> 11 beats, alpha2) fractal correlation properties and with approximate entropy of RR interval data in 38 patients with stable angina pectoris without previous myocardial infarction or cardiac medication at the time of the study and 38 age-matched healthy controls. The short- and long-term fractal scaling exponents (alpha1, alpha2) were significantly higher in the coronary patients than in the healthy controls (1.34 +/- 0.15 vs 1.11 +/- 0.12 [p <0.001] and 1.10 +/- 0.08 vs 1.04 +/- 0.06 [p <0.01], respectively), and they also had lower approximate entropy (p <0.05), standard deviation of all RR intervals (p <0.01), and high-frequency spectral component of HR variability (p <0.05). The short-term fractal scaling exponent performed better than other heart rate variability parameters in differentiating patients with coronary artery disease from healthy subjects, but it was not related to the clinical or angiographic severity of coronary artery disease or any single nonspectral or spectral measure of HR variability in this retrospective study. Patients with stable angina pectoris have altered fractal properties and reduced complexity in their RR interval dynamics relative to age-matched healthy subjects. Dynamic analysis may complement traditional analyses in detecting altered HR behavior in patients with stable angina pectoris.
The goal of this study was to investigate the alterations in blood pressure control in young spontaneously hypertensive rats (SHR), as reflected in the power distribution of blood pressure fluctuations. We studied six SHR preceding the onset of overt hypertension, compared to six age matched control rats, the normotensive Wistar-Kyoto rats (WKY), and analyzed the power density distribution of several blood pressure related signals, namely: arterial blood pressure (ABP), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and heart rate (HR). ABP fluctuations exhibited a basic difference in the power distribution pattern between the strains: at low frequencies (< 0.15 Hz) more power was observed in WKY than in SHR, while in the (0.35-1.00 Hz) range, more power was observed in SHR. These significant differences in patterns which existed at baseline, were abolished by prazosin (2.5 mg/kg). Observing the power distribution in the BP related signals, the patterns were different from that found in the ABP itself. At baseline, in SBP and DBP, the most dominant power was located at low frequencies < 0.04 Hz, like in ABP. However, unlike ABP, the remainder of the power was located in the high frequency region (HF: 1.5-3.0 Hz), mainly in SHR. Prazosin had a marked effect on PP power spectra; it shifted the power to the HF region in both strains. In PP, power spectra differences observed between the strains at baseline in HF were eliminated by prazosin. This seems to indicate that, in SHR compared to WKY, respiratory fluctuations which are low at baseline in PP, are a mechanical reflection of the higher sympathetic tone in SHR before alpha1 sympathetic blockade. This study supports previous findings in which differences in cardiovascular control occur in SHR already at the prehypertensive stage. The above results suggest that alpha1 sympathetic control is altered in the SHR strain, and therefore, when this limb is blocked, some of the differences between the strains disappear. Furthermore, the analysis of the BP related signals enable us to identify alterations existing in the control mechanisms in SHR, which involve adjunct control mechanisms enhanced under alpha1 sympathetic blockade. Finally, an important result is, that for all BP related signals under study, excluding HR, the response to alpha1-blockade reduces the power density in the 0.07-0.15 Hz region indicating that this region is directly associated with the activity of alpha control.
Shift work is associated with an increased rate of cardiovascular diseases and accidents. Discordance between circadian rhythms of stress-related biological variables and the work-sleep schedule might explain the reduced efficiency of work. It is not clear whether a shift schedule of work may induce similar discordance in the 24-hour oscillatory pattern of the cardiac autonomic control in respect to the work-sleep periods.
Twenty-two healthy male blue-collar shift workers underwent 24-hour ECG recordings during each of the 3 different shifts (first, 6 AM to 2 PM; second, 2 to 10 PM; third, 10 PM to 6 AM). Spectral analysis of heart rate variability over 24 hours provided the normalized markers of cardiac sympathetic (LF(nu)) and vagal (HF(nu)) modulation of the sinoatrial node activity and of the sympathovagal balance (LF/HF). LF(nu) and LF/HF exhibited 24-hour oscillations with different times of maximum and minimum in accordance with the working and sleeping periods, respectively. Lower values of LF(nu) and LF/HF suggestive of a reduced cardiac sympathetic modulation were present when the job task was performed at night compared with the values observed when the work was performed during morning and evening.
Continuous weekly changes of time of maximum and minimum in the cardiac sympathetic and vagal autonomic control may play a role in the excessive rate of cardiovascular diseases in shift workers. The reduced values of the indexes of cardiac sympathetic modulation during night work might be related to the presence of sleepiness or diminished alertness, which in turn could facilitate errors and accidents.
The physiological mechanisms mediating the variability and diurnal rhythm of blood pressure are unclear. We tested the hypothesis that resting sympathetic activity is linked to the variability characteristics and 24-hour profile of ambulatory blood pressure measurements. We evaluated the relationship between muscle sympathetic nerve activity (MSNA) and the level, variability, and nocturnal fall of ambulatory blood pressure in 69 normal men. Subjects were subdivided according to the tertiles of MSNA distributions. Mean 24-hour blood pressure was not significantly different across the 3 groups. Compared with subjects in the first tertile (lowest MSNA, <18 bursts/min), subjects in the third tertile (highest MSNA, >25 bursts/min) had significantly greater daytime blood pressure variability, whether expressed as absolute values (10.2+/-0.5 versus 8.1+/-0.4 mm Hg for systolic blood pressure and 9.4+/-0.4 versus 7.2+/-0.4 mm Hg for diastolic blood pressure; P<0.01 for both comparisons) or as variation coefficients (8.1+/-0.4% versus 6.6+/-0.3% for systolic blood pressure and 12.7+/-0.7% versus 10.1+/-0.6% for diastolic blood pressure; P<0.01 for both comparisons). Subjects in the third tertile also had a more striking absolute and percentage fall in systolic blood pressure from daytime to nighttime than subjects in the first tertile (17+/-2 versus 10+/-2 mm Hg, P=0.02, or 13+/-1% versus 8.2+/-1.4%, P=0.02). In conclusion, higher resting measurements of sympathetic traffic are associated with greater daytime blood pressure variability and a more marked nocturnal decline in blood pressure in normal subjects. These findings suggest that sympathetic neural mechanisms may contribute importantly to the regulation of blood pressure over the 24-hour period.