Genetic basis of blood pressure and hypertension

Blood pressure (BP) is a complex trait regulated by an intricate network of physiological pathways involving extracellular fluid volume homeostasis, cardiac contractility and vascular tone through renal, neural or endocrine systems. Untreated high BP, or hypertension (HTN), is associated with increased mortality, and thus a better understanding of the pathophysiological and genetic underpinnings of BP regulation will have a major impact on public health. However, identifying genes that contribute to BP and HTN has proved challenging. In this review we describe our current understanding of the genetic architecture of BP and HTN, which has accelerated over the past five years primarily owing to genome-wide association studies (GWAS) and the continuing progress in uncovering rare gene mutations, epigenetic markers and regulatory pathways involved in the physiology of BP. We also look ahead to future studies characterizing novel pathways that affect BP and HTN and discuss strategies for translating current findings to the clinic.     

Application of 1D blood flow models of the human arterial network to differential pressure predictions

A new application of 1D models of the human arterial network is proposed. We take advantage of the sensitivity of the models predictions for the pressure profiles within the main aorta to key model parameter values. We propose to use the patterns in the predicted differences from a base case as a way to infer to the most probable changes in the parameter values. We demonstrate this application using an impedance model that we have recently developed (Johnson, 2010). The input model parameters are all physiologically related, such as the geometric dimensions of large arteries, various blood properties, vessel elasticity, etc. and can therefore be patient specific. As a base case, nominal values from the literature are used. The necessary information to characterize the smaller arteries, arterioles, and capillaries is taken from a physical scaling model (West, 1999). Model predictions for the effective impedance of the human arterial system closely agree with experimental data available in the literature. The predictions for the pressure wave development along the main arteries are also found in qualitative agreement with previous published results. The model has been further validated against our own measured pressure data in the carotid and radial arteries, obtained from healthy individuals. Upon changes in the value of key model parameters, we show that the differences seen in the pressure profiles correspond to qualitatively different patterns for different parameters. This suggests the possibility of using the model in interpreting multiple pressure data of healthy/diseased individuals.     

癫痫电网络重建过程中的海马-体循环动脉血压调节网络

目的:观察右侧海马(HPC)微量注射印防己毒素(PTX)诱导HPC癫痫电网络重建过程中HPG体循环动脉血压调节网络的形成.方法:将PTX(7.2μg)微量注射到大鼠右侧HPC诱发HPC癫痫,四通道同步记录左侧深部电图、单个HPC细胞外单位放电、左侧股动脉血压和标准Ⅱ导联心电图.结果:将PTX微量注射到右侧HPC后可以引起以下效应:①对侧HPC神经元长时程爆发式单位放电与单位后放电,并具有相似的脉冲间隔(interspike intervals,ISI)点分布;②延迟对侧HPC神经元爆发式单位放电与相对应的股动脉血压下降发生的时间关系;③出现复合式的对侧HPC神经元爆发式单位放电或单位后放电和股动脉血压下降耦合;④具有相似点分布特征的对侧HPC网络波峰间隔(interpeak intervals,IPI)和单个神经元ISI共同参与了HPC-体循环动脉血压调节网络的构成.结论:将PTX微量注射到右侧HPC可以在诱导对侧HPC癫痫网络形成的同时通过特征性的瞬时编码形式调制HPC-体循环动脉血压调节网络的功能活动.     

Comparative study of unidirectional transducers for invasive blood pressure monitoring

This paper reports on the results of a study in which the offset drift, sensitivity error and drift, as well as the linearity error of six DPT's were investigated under normal ambient conditions and varying conditions of temperature, light, operating time and variation of supply voltage. In addition, the dynamic response, and the influence of storage at extreme temperatures, and resterilisation, was examined. The electrical and mechanical safety/reliability of DPT's was also investigated. The results obtained are compared.     

Animal models for the study of arterial hypertension

Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.     

Comparative accuracy of two new electronic devices for the noninvasive determination of blood pressure

Recent developments in behavioral approaches to cardiovascular disease have called for physiological monitoring devices that reduce experimenter bias, are easy to operate, can be used ambulatorily, and/or provide ongoing, automated monitoring of pertinent cardiovascular functions--i.e., blood pressure and heart rate. Neither the invasive monitoring (via catheterization) nor the standard auscultatory method of blood pressure determination, however, has these characteristics. In the present study, two new methods/devices--(1) a low-weight, low-cost, battery-operated sphygmomanometer (SM), and (2) a more expensive automated electronic SM with electrical pump-are compared with each other and with the more common auscultatory method and a standard mercury SM. Both new devices were also compared with a standard pulse count. Data were derived from 10 readings of 10 healthy subjects each across the three possible comparisons, thus totaling N = 30. Correlation coefficients and average differences were computed and indicated high intercorrelations (between r = .89 and r = .99) between each pairing of the new electronic devices and the mercury SM. Intercorrelations of blood pressure determination with the two new electronic devices, however, were only moderate. Potential reasons for the variability are discussed, and guidelines for the optimal use of the new, easy-to-operate electronic devices are presented.     

Comparative accuracy of two new electronic devices for the noninvasive determination of blood pressure

Recent developments in behavioral approaches to cardiovascular disease have called for physiological monitoring devices that reduce experimenter bias, are easy to operate, can be used ambulatorily, and/or provide ongoing, automated monitoring of pertinent cardiovascular functions—i.e., blood pressure and heart rate. Neither the invasive monitoring (via catheterization) nor the standard auscultatory method of blood pressure determination, however, has these characteristics. In the present study, two new methods/devices — (1) a low-weight, low-cost, battery-operated sphygmomanometer (SM), and (2) a more expensive automated electronic SM with electrical pump — are compared with each other and with the more common auscultatory method and a standard mercury SM. Both new devices were also compared with a standard pulse count. Data were derived from 10 readings of 10 healthy subjects each across the three possible comparisons, thus totalingN=30. Correlation coefficients and average differences were computed and indicated high intercorrelations (betweenr=.89 andr=.99) between each pairing of the new electronic devices and the mercury SM. Intercorrelations of blood pressure determination with the two new electronic devices, however, were only moderate. Potential reasons for the variability are discussed, and guidelines for the optimal use of the new, easy-to-operate electronic devices are presented.     

Circadian time-qualified tolerance intervals for ambulatory blood pressure monitoring in the diagnosis of hypertension

The large-amplitude circadian pattern in blood pressure of healthy subjects of both genders suggests that the constant threshold currently used to diagnose hypertension should be replaced by a time-specified reference limit reflecting the mostly predictable blood pressure variability during the 24 h. Accordingly, we derived circadian time-specified reference standards for blood pressure as a function of gender. We studied 743 normotensive Caucasian volunteers (400 men and 343 women), 45.7 ± 16.5 (mean ± SD) years of age. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual in order to avoid differences among subjects in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each gender separately. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data and, therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results reflect expected changes in the tolerance limits as a function of gender and circadian sampling time, as well as upper blood pressure limits below the thresholds currently used for diagnosing hypertension, especially for women. The use of these time-dependent tolerance limits for the computation of a hyperbaric index as a measure of blood pressure excess has already been shown to provide a reproducible and high-sensitivity test for the diagnosis of hypertension, which can also be used to evaluate treatment efficacy.     

Fitting of dynamic recurrent neural network models to sensory stimulus-response data

We present a theoretical study aiming at model fitting for sensory neurons. Conventional neural network training approaches are not applicable to this problem due to lack of continuous data. Although the stimulus can be considered as a smooth time-dependent variable, the associated response will be a set of neural spike timings (roughly the instants of successive action potential peaks) that have no amplitude information. A recurrent neural network model can be fitted to such a stimulus-response data pair by using the maximum likelihood estimation method where the likelihood function is derived from Poisson statistics of neural spiking. The universal approximation feature of the recurrent dynamical neuron network models allows us to describe excitatory-inhibitory characteristics of an actual sensory neural network with any desired number of neurons. The stimulus data are generated by a phased cosine Fourier series having a fixed amplitude and frequency but a randomly shot phase. Various values of amplitude, stimulus component size, and sample size are applied in order to examine the effect of the stimulus to the identification process. Results are presented in tabular and graphical forms at the end of this text. In addition, to demonstrate the success of this research, a study involving the same model, nominal parameters and stimulus structure, and another study that works on different models are compared to that of this research.     

Role of zinc in regulation of arterial blood pressure and in the etiopathogenesis of arterial hypertension

Increased gastrointestinal absorption and urinary excretion of zinc has been confirmed in experimental and clinical studies on primary arterial hypertension as a result from changes of intracellular and extracellular zinc content. In arterial hypertension, the levels of zinc in serum, lymphocyte, and bone decrease while increasing in heart, erythrocytes, kidney, liver, suprarenal glands and spleen. These changes result in the loss of zinc homeostasis that leads to various degrees of deficiency, not entirely compensated by nutritional factors or increased absorption in the gastrointestinal tract. Loss of zinc homeostasis can be both cause and effect of high blood pressure. In the present review, the role of zinc metabolism changes and its mechanisms in arterial hypertension are discussed.     

Fenofibrate lowers blood pressure in two genetic models of hypertension

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate.     

Ultradian rhythmic models of blood pressure variation in normal human daily life

To examine levels and variance structure of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR), we measured those 3 variables every 7.5 min for 24 h (approximately 192 samples each subject) by ambulatory monitoring in 2 nominated groups of normal volunteers: younger (Y; 8 men, 5 women, 24-44 years) and older (O; 13 men, 12 women, 50-95 years). Y and O did not differ in either sleep or wake means for HR and DBP. Mean SBP in O was 17 mm Hg higher than in Y during wakefulness. Thirty-four subjects had significant low frequency variations (presumably the circadian rhythm) in SBP, DBP and HR, regardless of age. A periodic model fitting the time series required a 9 h feature (rhythm) for Y and O in DBP for best reduction of mean square error. In addition, O regularly showed 3 h features in both SBP and DBP, a 6 h feature in DBP and a 9 h feature in SBP, which were absent in Y. Our results suggest that low-power ultradian rhythms may appear in both SBP and DBP after age 50, and possibly serve as dynamic markers of normal cardiovascular aging.     

老年心血管危重患者有创与无创血压监测对比研究

目的比较老年心血管危重患者有创与无创血压同一时间段测量值的差异。方法对31例患者同一时间进行有创与无创血压测定,测压时间为入住ICU后30min及1、2、3h共4次,并对同一患者同一时间同时监测右侧有创血压与对侧无创血压平均差值进行分析比较。结果有创血压值比无创血压值高。结论临床上在治疗和抢救老年心血管危重患者时应考虑到有创与无创血压的差异,慎重处理。     

The BpTRU automatic blood pressure monitor compared to 24 hour ambulatory blood pressure monitoring in the assessment of blood pressure in patients with hypertension

Background

Increasing evidence suggests that ABPM more closely predicts target organ damage than does clinic measurement. Future guidelines may suggest ABPM as routine in the diagnosis and monitoring of hypertension. This would create difficulties as this test is expensive and often difficult to obtain. The purpose of this study is to determine the degree to which the BpTRU automatic blood pressure monitor predicts results on 24 hour ambulatory blood pressure monitoring (ABPM).

Methods

A quantitative analysis comparing blood pressure measured by the BpTRU device with the mean daytime blood pressure on 24 hour ABPM. The study was conducted by the Centre for Studies in Primary Care, Queen's University, Kingston, Ontario, Canada on adult primary care patients who are enrolled in two randomized controlled trials on hypertension. The main outcomes were the mean of the blood pressures measured at the three most recent office visits, the initial measurement on the BpTRU-100, the mean of the five measurements on the BpTRU monitor, and the daytime average on 24 hour ABPM.

Results

The group mean of the three charted clinic measured blood pressures (150.8 (SD10.26) / 82.9 (SD 8.44)) was not statistically different from the group mean of the initial reading on BpTRU (150.0 (SD21.33) / 83.3 (SD12.00)). The group mean of the average of five BpTRU readings (140.0 (SD17.71) / 79.8 (SD 10.46)) was not statistically different from the 24 hour daytime mean on ABPM (141.5 (SD 13.25) / 79.7 (SD 7.79)). Within patients, BpTRU average correlated significantly better with daytime ambulatory pressure than did clinic averages (BpTRU r = 0.571, clinic r = 0.145). Based on assessment of sensitivity and specificity at different cut-points, it is suggested that the initial treatment target using the BpTRU be set at <135/85 mmHG, but achievement of target should be confirmed using 24 hour ABPM.

Conclusion

The BpTRU average better predicts ABPM than does the average of the blood pressures recorded on the patient chart from the three most recent visits. The BpTRU automatic clinic blood pressure monitor should be used as an adjunct to ABPM to effectively diagnose and monitor hypertension.     

Artificial arterial blood pressure artifact models and an evaluation of a robust blood pressure and heart rate estimator

Background  

Within the intensive care unit (ICU), arterial blood pressure (ABP) is typically recorded at different (and sometimes uneven) sampling frequencies, and from different sensors, and is often corrupted by different artifacts and noise which are often non-Gaussian, nonlinear and nonstationary. Extracting robust parameters from such signals, and providing confidences in the estimates is therefore difficult and requires an adaptive filtering approach which accounts for artifact types.     

Ambulatory blood pressure monitoring: assessing the diurnal variation of blood pressure

The purposes of this paper are to examine the effects of activity, situation of measurement, mood, and occupation on the daily variation of blood pressure and to discuss the potential utility of ambulatory blood pressure monitoring in physical anthropological studies. The subjects of the blood pressure variability study are 125 men who were referred to the Hypertension Center at New York Hospital--Cornell Medical Center for evaluation of hypertension. There were 1,386 blood pressure measurements from these subjects available for study, which were taken using noninvasive ambulatory blood pressure monitoring techniques. Pressures were transformed to z scores using the subject's daily mean pressure and standard deviation to assess the relative elevation during the experience of the various factors. The results show that activity and mood are the most significant sources of blood pressure variation (P less than .005) and are additive. Occupation, which may be an indicator of social class in this population, also modified the mood effects. Because ambulatory blood pressure monitors obtain many readings over a day under a variety of circumstances, their use can improve epidemiological and human biological studies of the inheritance and variability of blood pressure. Ambulatory blood pressure monitoring is an important new tool in the study of human biological variation.