Blood pressure and heart rate variability are linked with hyperphosphatemia in chronic kidney disease patients

ABSTRACT

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and is associated with cardiovascular disease (CVD), which has contributed to an increase in mortality of CKD patients. The onset of CVD often varies by time-of-day. Acute myocardial infarction or ventricular arrhythmia occurs most frequently during early morning. Blood pressure (BP) and heart rate circadian rhythms account for the diurnal variations in CVD. Preservation of normal circadian time structure from the cardiomyocyte level to the whole organ system is essential for cardiovascular health and CVD prevention. Independent risk factors, such as reduced heart rate variability (HRV) and increased BP variability (BPV), are particularly prevalent in patients with CKD. Analysis of HRV is an important clinical tool for characterizing cardiac autonomic status, and reduced HRV has prognostic significance for various types of CVD. Circadian BP rhythms are classified as extreme dipper, dipper, non-dipper or riser. It has been reported that nocturnal riser BP pattern contributes to cardiovascular threats. Previous studies have indicated that the circadian rhythm of serum phosphate in CKD patients is consistent with the general population, with the highest diurnal value observed in the early morning hours, followed by a progressive decrease to the lowest value of the day, which occurs around 11:00 am. Rhythm abnormalities have become the main therapeutic target for treating CVD in CKD patients. It has been reported that high levels of serum phosphate are associated with reduced HRV and increased BPV in CKD patients. However, the mechanisms related to interactions between hyperphosphatemia, HRV and BPV have not been fully elucidated. This review focuses on the evidence and discusses the potential mechanisms related to the effects of hyperphosphatemia on HRV and BPV.     

Blood pressure and heart rate determination by radiotelemetry in mice

Mice are not commonly used in cardiovascular physiology, especially in space physiology because of methodological problems. The initial studies that have monitored arterial pressure and heart rate in mice used the tail cuff plethysmography method or classical catheterization techniques with a catheter liable to an external pressure transducer. But for long term arterial pressure measurements the studies have been facilitated by the development of radiotelemetry. This is a less constraining method as classical one allowing to monitor in continuous in freely moving animal blood pressure, heart rate and temperature. This technique allows to record these parameters thank to an implanted transmitter without physical connection with the monitoring system. The aim of this work was to valid the use of the radiotelemetry in mice to evaluate arterial blood pressure and heart rate during different stress conditions (but only control data are described in this paper).     

Differences between heart rate and blood pressure variability in schizophrenia.

Heart rate and blood pressure variability parameters were assessed to determine the risk of cardiac mortality in schizophrenia. We investigated 21 acute, unmedicated patients with paranoid schizophrenia and 21 matched controls. Cardiovascular parameters obtained included heart rate variability, blood pressure variability, cardiac output and left ventricular work index. All parameters investigated were analyzed using linear and non-linear techniques. These investigations revealed increased left ventricular work index and reduced heart rate variability. Furthermore, blood pressure was significantly higher compared to controls, whereas its variability was unchanged. We conclude that our results reflect autonomic cardiovascular dysregulation in acute schizophrenia.     

Short-term and long-term blood pressure and heart rate variability in the mouse

Knowledge on murine blood pressure and heart rate control mechanisms is limited. With the use of a tethering system, mean arterial pressure (MAP) and pulse interval (PI) were continuously recorded for periods up to 3 wk in Swiss mice. The day-to-day variation of MAP and PI was stable from 5 days after surgery. Within each mouse (n = 9), MAP and PI varied by 21+/-6 mm Hg and 17+/-4 ms around their respective 24-h averages (97+/-3 mm Hg and 89+/-3 ms). Over 24-h periods, MAP and PI were bimodally distributed and clustered around two preferential states. Short-term variability of MAP and PI was compared between the resting (control) and active states using spectral analysis. In resting conditions, variability of MAP was mainly confined to frequencies <1 Hz, whereas variability of PI was predominantly linked to the respiration cycle (3-6 Hz). In the active state, MAP power increased in the 0.08- to 3-Hz range, whereas PI power fell in the 0.08- to 0.4-Hz range. In both conditions, coherence between MAP and PI was high at 0.4 Hz with MAP leading the PI fluctuations by 0.3-0.4 s, suggesting that reflex coupling between MAP and PI occurred at the same frequency range as in rats. Short-term variability of MAP and PI was studied after intravenous injection of autonomic blockers. Compared with the resting control state, MAP fell and PI increased after ganglionic blockade with hexamethonium. Comparable responses of MAP were obtained with the alpha-blocker prazosin, whereas the beta-blocker metoprolol increased PI similarly. Muscarinic blockade with atropine did not significantly alter steady-state levels of MAP and PI. Both hexamethonium and prazosin decreased MAP variability in the 0.08- to 1-Hz range. In contrast, after hexamethonium and metoprolol, PI variability increased in the 0.4- to 3-Hz range. Atropine had no effect on MAP fluctuations but decreased those of PI in the 0.08- to 1-Hz range. These data indicate that, in mice, blood pressure and its variability are predominantly under sympathetic control, whereas both vagal and sympathetic nerves control PI variability. Blockade of endogenous nitric oxide formation by N(G)-nitro-L-arginine methyl ester increased MAP variability specifically in the 0.08- to 0.4-Hz range, suggesting a role of nitric oxide in buffering blood pressure fluctuations.     

Blood pressure and heart rate variability response to noninvasive ventilation in patients with exacerbations of chronic obstructive pulmonary disease

Sympathetic activation and parasympathetic withdrawal are commonly observed during acute exacerbations of chronic obstructive pulmonary disease (COPD). We have demonstrated previously that noninvasive positive-pressure ventilation (NPPV) improves parasympathetic neural control of heart rate in patients with obstructive sleep apnea. We hypothesized that NPPV may exert such beneficial effects in COPD as well. Therefore, we assessed the acute effects of NPPV on systemic blood pressure and indexes of heart rate variability (HRV) in 23 patients with acute exacerbations of COPD. The measurements of HRV in the frequency domain were computed by an autoregressive spectral technique. The use of NPPV resulted in significant increases of oxygen saturation (from 89.2+/-1.0 to 92.4+/-0.9 %, p<0.001) in association with reductions in systolic and diastolic blood pressures and heart rate (from 147+/-3 to 138+/-3 mm Hg, from 86+/-2 to 81+/-2 mm Hg, from 85+/-3 to 75+/-2 bpm, p<0.001 for all variables), and increases in ln-transformed high frequency band of HRV (from 6.4+/-0.5 to 7.4+/-0.6 ms(2)/Hz, p<0.01). Reductions in heart rate and increases in ln-transformed HF band persisted after NPPV withdrawal. In conclusion, these findings suggest that NPPV may cause improvements in the neural control of heart rate in patients with acute exacerbations of COPD.     

Blood pressure and heart rate during rest-exercise and exercise-rest transitions

The transients of mean arterial blood pressure (BPa) and heart rate (fc) during rest-exercise and exercise-rest transitions have been studied in six healthy sport students. After 5 min of rest in an upright position on a cycle ergometer they exercised for 15 min and remained seated for a further 5 min. The subjects exercised at four different constant intensities (40 W, 80 W, 120 W, 160 W) in random order separated by at least 24 h. The BPa was determined by a noninvasive and continuous method. During the first minute of exercise, three phases of response could be distinguished, with the first two showing no clear relationship to intensity. Phase 1 consisted of simultaneous increases in both fc and BP during the first 6 s. In phase 2, BPa decreased while fc continued to increase. During phase 3, BPa and fc approximated constant values or a linear increase. Both parameters showed no comparable intensity-independent reactions during the off-transients. In conclusion, during the first 15 s of rest-exercise transitions there seems to be a fast and uniform cardiovascular drive which overrode other influences on fc.     

Age dependency and correlation of heart rate variability,blood pressure variability and baroreflex sensitivity

Simultaneous analysis of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) with different types of measures may provide non-duplicative information about autonomic cardiovascular regulation. Therefore, a multiple signal analysis of cardiovascular time series will enhance the physiological understanding of neuro cardiovascular regulation with deconditioning in bedrest or related gravitational physiological studies. It has been shown that age is an important determinant of HRV and BRS in healthy subjects. Whereas in the case of BPV, the effect of aging seems to depend upon the activity status of the subjects. In view of the facts that most of the previous works were dealing with only the variability of one kind of cardiovascular parameters in one study with conventional time-domain and/or frequency-domain analysis, we therefore designed the present work to compare the HRV, BPV and BRS between young and middle-aged male healthy subjects in one study with the same subjects using various techniques, including the approximate entropy (ApEn) measurement, a statistic quantifying HRV "complexity" derived from non-linear dynamics.     

Blood pressure and heart rate and withdrawal of antihypertensive drugs.

The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets.     

Frequency-dependent baroreflex modulation of blood pressure and heart rate variability in conscious mice

The goal of this study was to determine the baroreflex influence on systolic arterial pressure (SAP) and pulse interval (PI) variability in conscious mice. SAP and PI were measured in C57Bl/6J mice subjected to sinoaortic deafferentation (SAD, n = 21) or sham surgery (n = 20). Average SAP and PI did not differ in SAD or control mice. In contrast, SAP variance was enhanced (21 +/- 4 vs. 9.5 +/- 1 mmHg2) and PI variance reduced (8.8 +/- 2 vs. 26 +/- 6 ms2) in SAD vs. control mice. High-frequency (HF: 1-5 Hz) SAP variability quantified by spectral analysis was greater in SAD (8.5 +/- 2.0 mmHg2) compared with control (2.5 +/- 0.2 mmHg2) mice, whereas low-frequency (LF: 0.1-1 Hz) SAP variability did not differ between the groups. Conversely, LF PI variability was markedly reduced in SAD mice (0.5 +/- 0.1 vs. 10.8 +/- 3.4 ms2). LF oscillations in SAP and PI were coherent in control mice (coherence = 0.68 +/- 0.05), with changes in SAP leading changes in PI (phase = -1.41 +/- 0.06 radians), but were not coherent in SAD mice (coherence = 0.08 +/- 0.03). Blockade of parasympathetic drive with atropine decreased average PI, PI variance, and LF and HF PI variability in control (n = 10) but had no effect in SAD (n = 6) mice. In control mice, blockade of sympathetic cardiac receptors with propranolol increased average PI and decreased PI variance and LF PI variability (n = 6). In SAD mice, propranolol increased average PI (n = 6). In conclusion, baroreflex modulation of PI contributes to LF, but not HF PI variability, and is mediated by both sympathetic and parasympathetic drives in conscious mice.     

Spectral analysis of the heart rate,blood pressure,and respiratory rate variability in 8- to 11-year-old children at rest

Spectral analysis was performed to assess the periodic variations in the heart rate (HR), blood pressure (BP), and respiratory volume (RV) in 8- to 11- year-old children at rest. Age- and gender-related differences were revealed in the total power and spectral components of the HR, BP, and RV spectra.Translated from Fiziologiya Cheloveka, Vol. 31, No. 1, 2005, pp. 33–39.Original Russian Text Copyright © 2005 by Kuznetsova, Sonkin.     

Impact of acute hypoxia on heart rate and blood pressure variability in conscious dogs

To examine whether the impacts of hypoxia on autonomic regulations involve the phasic modulations as well as tonic controls of cardiovascular variables, heart rate, blood pressure, and their variability during isocapnic progressive hypoxia were analyzed in trained conscious dogs prepared with a permanent tracheostomy and an implanted blood pressure telemetry unit. Data were obtained at baseline and when minute ventilation (VI) first reached 10 (VI10), 15 (VI15), and 20 (VI20) l/min during hypoxia. Time-dependent changes in the amplitudes of the high-frequency component of the R-R interval (RRIHF) and the low-frequency component of mean arterial pressure (MAPLF) were analyzed by complex demodulation. In a total of 47 progressive hypoxic runs in three dogs, RRIHF decreased at VI15 and VI20 and MAPLF increased at VI10 and VI15 but not at VI20, whereas heart rate and arterial pressure increased progressively with advancing hypoxia. We conclude that the autonomic responses to isocapnic progressive hypoxia involve tonic controls and phasic modulations of cardiovascular variables; the latter may be characterized by a progressive reduction in respiratory vagal modulation of heart rate and a transient augmentation in low-frequency sympathetic modulation of blood pressure.     

Blood pressure and heart rate in patients with ischaemic heart disease receiving nifedipine and propranolol.

A randomised controlled crossover trial was performed to assess the anti-anginal effects of nifedipine and propranolol separately and together. The effects of these treatments on blood pressure and heart rate were assessed at rest and after the cold pressor and mental arithmetic tests. Nifedipine and propranolol together produced the greatest reduction in supine and erect systolic and diastolic blood pressures. Propranolol (480 mg daily) lowered resting systolic/diastolic blood pressures by 7/6 mm Hg and nifedipine (60 mg daily) lowered it by 10/8 mm Hg, while in the erect position the hypotensive effect of these agents averaged 9/8 mm Hg. During the cold pressor test propranolol lowered the maximum pressure by an average of 11/6 mm Hg and nifedipine by 19/10 mm Hg. For the mental arithmetic test, the results were 7/2 mm Hg and 16/7 mm Hg respectively. Propranolol (480 mg daily)reduced supine and erect heart rate by 19 and 25 beats/minute respectively, while nifedipine did not alter heart rate significantly. The favourable haemodynamic responses to nifedipine suggest that it may be of value in the management of hypertension.     

Effects of 12-hour rotating shifts on menstrual cycles of photoelectronic workers in Taiwan

12 h rotating shifts are common in high-tech industries in Taiwan. The aim of this longitudinal study was to evaluate the effect of the disruption of circadian rhythms by the shift schedule on menstrual cycle length (MCL) and regularity of female workers at an optoelectronic company in Taiwan. We recruited females who worked rotating shifts in a clean room environment as the shift-work group and female office workers who worked normal business hours as the comparison group. Every participant recorded their MCL for each menstruation cycle up to eight consecutive months prospectively and provided demographic characteristics, reproductive history, and menstrual characteristics. We collected data on 1,135 and 117 menstruation cycles in the shift-work (n = 280) and comparison groups (n = 49). Whereas the two groups had similar group means for MCL and number of menstrual bleeding days, the prevalence of menstrual cycle irregularity (cycles <25 or >35 days) was higher in the shift-work group ( p = 0.04). Univariate and multivariate logistic regression analyses demonstrated that rotating shift work was an independent predictor of menstrual cycle irregularity (odds ratio = 1.71, 95% confidence interval: 1.03-2.88) after adjusting for shift-work history, employment duration, coffee consumption,and pre-employment menstrual cycle irregularity. Although further study is required to confirm our findings plus to explore prevention and control measures, our data indicate rotating shift work can increase the risk of MCL irregularity.     

Resting heart rate,heart rate variability and functional decline in old age

Background:

Heart rate and heart rate variability, markers of cardiac autonomic function, have been linked with cardiovascular disease. We investigated whether heart rate and heart rate variability are associated with functional status in older adults, independent of cardiovascular disease.

Methods:

We obtained data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). A total of 5042 participants were included in the present study, and mean follow-up was 3.2 years. Heart rate and heart rate variability were derived from baseline 10-second electrocardiograms. Heart rate variability was defined as the standard deviation of normal-to-normal RR intervals (SDNN). Functional status in basic (ADL) and instrumental (IADL) activities of daily living was measured using Barthel and Lawton scales, at baseline and during follow-up.

Results:

The mean age of the study population was 75.3 years. At baseline, higher heart rate was associated with worse ADL and IADL, and lower SDNN was related to worse IADL (all p values < 0.05). Participants in the highest tertile of heart rate (range 71–117 beats/min) had a 1.79-fold (95% confidence interval [CI] 1.45–2.22) and 1.35-fold (95% CI 1.12–1.63) higher risk of decline in ADL and IADL, respectively (p for trend < 0.001 and 0.001, respectively). Participants in the lowest tertile of SDNN (range 1.70–13.30 ms) had 1.21-fold (95% CI 1.00–1.46) and 1.25-fold (95% CI 1.05–1.48) higher risk of decline in ADL and IADL, respectively (both p for trends < 0.05). All associations were independent of sex, medications, cardiovascular risk factors and comorbidities.

Interpretation:

Higher resting heart rate and lower heart rate variability were associated with worse functional status and with higher risk of future functional decline in older adults, independent of cardiovascular disease. This study provides insight into the role of cardiac autonomic function in the development of functional decline.Elevated heart rate and reduced heart rate variability — the beat-to-beat variation in heart rate intervals — both reflect an altered balance of the autonomic nervous system tone characterized by increased sympathetic and/or decreased parasympathetic activity.^1–3 Sympathetic overactivity has been linked to a procoagulant state and also to risk factors for atherosclerosis, including metabolic syndrome, obesity and subclinical inflammation.^2–4 Moreover, increased heart rate is related to atherosclerosis, not only as an epiphenomenon of sympathetic overactivity, but also through hemodynamic mechanisms, such as high pulsatile shear stress, which leads to endothelial dysfunction.⁵Atherosclerosis has been linked to increased risk of functional decline in older people via cardiovascular events.⁶ As the world population is aging, the burden of functional disability is expected to increase.⁶ It has been hypothesized that heart rate and heart rate variability are markers of frailty, an increased vulnerability to stressors and functional decline.⁷ However, the direct link between these 2 parameters and risk of functional decline has not been fully established, and it is uncertain whether this association is independent of cardiovascular comorbidities.In this study, we examined whether heart rate and heart rate variability were cross-sectionally and longitudinally associated with functional status in older adults at high risk of cardiovascular disease, independent of cardiovascular risk factors and comorbidities.     

The genetic contribution to heart rate and heart rate variability in quiescent mice

Recent studies have suggested a genetic component to heart rate (HR) and HR variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Electrocardiogram data were recorded from 30 strains of inbred mice and 29 RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low-frequency (LF) and high-frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genomewide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated HR 1 (Hr1)]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated HRV-high-frequency 1 (Hrvhf1)] and three suggestive QTLs on chromosomes 2, 11 and 15. In conclusion, the results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. A lack of correlation between HR and HRV phenotypes in some inbred strains suggests that different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest.     

Mechanisms of blood pressure and heart rate variability: an insight from low-level paraplegia

It is still unclear whether the low-frequency oscillation in heart rate is generated by an endogenous neural oscillator or by a baroreflex resonance. Our aim was to investigate this issue by analyzing blood pressure and heart rate variability and the baroreflex function in paraplegic subjects with spinal cord injury below the fourth thoracic vertebra. These subjects were selected because they represent a model of intact central neural drive to the heart, with a partially impaired autonomic control of the vessels. In our study, arterial blood pressure and ECG were recorded in 33 able-bodied controls and in 33 subjects with spinal cord lesions between the fifth thoracic and the fourth lumbar vertebra 1) during supine rest (lowest sympathetic activation), 2) sitting on a wheelchair (light sympathetic activation), and 3) during exercise (moderate sympathetic activation). Blood pressure and heart rate spectra, coherence, and baroreflex function (sequence technique) were estimated in each condition. Compared with controls, paraplegic subjects showed a reduction of the low-frequency power of blood pressure and heart rate, and, unlike controls, a 0.1-Hz peak did not appear in their spectra. Sympathetic activation increased the 0.1-Hz peak of blood pressure and heart rate and the coherence at 0.1 Hz in controls only. Paraplegic subjects also had significantly lower baroreflex effectiveness and greater blood pressure variability. In conclusion, the disappearance of the 10-s oscillation of heart rate and blood pressure in subjects with spinal cord lesion supports the hypothesis of the baroreflex nature of this phenomenon.     

Initial heart rate variability and radiosensitivity in rabbits

The goal of the work was to investigate the rabbits' radiosensitivity dependence on the initial functional state of the autonomous nervous system (ANS), as assessed by time-frequency parameters of the heart rate variability (HRV). Survival rate and rhythm-cardiologic correlates of the pathological processes following total X-irradiation, at doses of 2 and 12 Gy, were studied with an aid of modern computer technologies of measurement and data analysis. It has been found that the animals with initial prevailing of adrenergic influences on the HRV ("sympathicotonics") are significantly more sensitive to irradiation than those in which the parasympathetic prevalence was evident ("vagotonics"). The most characteristic and determining difference between these two groups of animals is initial level of the sum regulatory influences on the heart rhythm, which is manifested in value of total power of spectral density (TP) of HRV. In the sympathicotonics the TP is significantly lower than in the vagotonics. The primary HRV response to irradiation practically does not differ according to the dose and manifests in sharp suppression of the TP in both groups of the animals. At 12 Gy this process is irreversible. In the sympathicotonics it develops earlier and terminates with death much sooner than in the vagotonics. An average life-span of the rabbits, at this dose, is 18.8 +/- 2.6 days in vagotonics, and 10.3 +/- 1.3 days in sympathicotonics (p < 0.02). At 2 Gy initial sharp decrease of the TP in the vagotonics lasts one week only. Then the sum regulatory influence of the ANS on the heart rate increases (rebound) and this condition, which probably points at general resistance of the organism, could be seen within two months; at the end of third month it stabilizes at the initial level. In the sympathycotonics initial sharp decrease of the TP also occurred, however no rebound was observed. The results obtained show that low initial level of the TP of HRV is sufficiently correct marker for higher radiosensitivity in the sympathotonic rabbits against the vagotonic ones.     

Mathematical model of heart rate variability

The study presents a mathematical model of non-linear dynamics of the heart rate variability (HRV). The model is based on quantitative characteristics of pulse conduction in the heart conducting system: the delays of sinoatrial (SA) and atrioventricular (AV) pulse conduction and refractors periods of the SA and AV nodes. The model predicts heart rate disturbances in fast electric activity of the atria, increase in the delay of the AV conduction, the critical value of atrial period where transition to non-linear dynamics of the heart rate variability starts. The correlation between indexes of HRV and period of stimulation of atria for 1-contour cardiac control model has been demonstrated.