Temporal cardiovascular causality during orthostatic stress by extended partial directed coherence.

sponsorship: The European Union (HEALTH-F7-2011-278249 EU-MASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council Advanced Researcher Grant 294713 EPLORE) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.0880.13) currently support the Studies Coordinating Centre (Leuven, Belgium). (European Union|HEALTH-F7-2011-278249 EU-MASCARA, European Union|HEALTH-F7-305507 HOMAGE, European Union (European Research Council)|294713 EPLORE, Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium|G.0881.13, Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium|G.0880.13)

The aim of the present study was to test the effects of different body on BP readings in a Turkish healthy young adults. It is known that many factors influence an individual's blood pressure measurement. However, guideliness for accurately measuring blood pressure inconsistently specify that patient's position and they should keep feet flat on the floor. Although there are more information on arm position in blood pressure measurement, surprisingly little information can be found in the literature with respect to the influence of body position on the blood pressure readings in healthy young people. A total of 157 healthy young students who had accepted to participate in the study were randomly selected. In all subjects the blood pressure was measured subsequently in four positions: Sitting blood pressure was taken from the left arm, which was flexed at the elbow and supported at the heart level on the chair. After at least one minute of standing, the blood pressure was then taken standing, with the arm supported at the elbow and the cuff at the heart level. After one minute of rest, the blood pressure was subsequently taken supine position. Finally, after one minute the blood pressure was again taken in this last position with supine position with crossed legs. The blood pressure tended to drop in the standing position compared with the sitting, supine and supine with crossed legs. Systolic and diastolic blood pressure was the highest in supine position when compared the other positions. There was a difference between systolic blood pressures and this was statistically significant (P < 0.001) but the difference between diastolic blood pressure was not statistically significant (P > 0.05). All changes in systolic blood pressure were statistically significant except those from supine to supine position with crossed legs. When assessing blood pressure it is important to take the position of the patient into consideration. Also, blood pressure measurement must be taken in sitting position with the arms supported at the right a trial level.

It takes two to tango: the coherence of cardiac output and sympathetic nerve activity

Although Heart Period (HP) variability is the most widely used measure to assess cardiovascular oscillations, its evaluation combined with that of Pulse Arrival Time (PAT) variability may provide additional information about cardiac dynamics and cardiovascular interactions. In this study, we computed the transfer entropy from PAT to HP in 76 subjects monitored at rest and during orthostatic and mental stress using both a model-free (k-Nearest Neighbors) and a linear parametric estimator. Our results show how the information flow between these two variables depends on the physiological condition and how the nonlinear measure captures more information than the linear one during orthostatic stress.

Blood Pressure Goals: How Low Is Safe in CKD?

Adverse childhood experiences (ACEs) represent psychosocial stressors that occur during critical developmental periods and are associated in a dose‐dependent manner with adverse cardiovascular outcomes in emerging adults, including greater age‐related increases in blood pressure (BP) and increased circulating endothelin‐1 (ET‐1), a psychosocial stress‐responsive, endothelium‐derived peptide and potent vasoconstrictor. ACEs have also been linked to lower resilience and hope, which is a motivational state based on goal‐directed energy (agency) and goal planning (pathways). Importantly, resilience and hope are each stable psychological traits that may protect against adversity. We examined the effects of a structured, progressive exercise training program on hope agency, hope pathways, resilience, BP, and circulating ET‐1 in young adult women with a history of moderate‐to‐severe (e.g., 4 or more) adverse childhood experiences (ACEs). We hypothesized that exercise training would increase resilience and hope, but lower systolic BP (SBP), diastolic BP (DBP), and circulating ET‐1. We further hypothesized that changes in hope and resilience would be associated with changes in BP and ET‐1 across the intervention period in the young women with ACEs. Forty‐two otherwise healthy young adult women with either four or more (ACE+) or with no ACEs (ACE–) were recruited and completed this study. Participants with ACEs (ACE+) were randomly assigned to either an exercise (n=14) or non‐exercise (n=14) control group, whereas women without a history of ACEs (ACE–) were assigned to a non‐exercise control (e.g., negative control group; n=14). Statistical analyses included two‐way mixed (group x time) effects and bivariate correlational analyses. Changes are reported as means ± SE. Agency did not change in any group (p = 0.14), but pathways improved only in the ACE+ exercise group (+1.6 ± 0.74 au; p = 0.03). ET‐1 decreased in the ACE+ exercise group only (‐0.31 ± 0.29 pg/ml, p= 0.04). While the interactions for resilience and SBP did not reach significance (p = 0.06 and 0.05, respectively), forced post‐hoc analyses indicated that resilience improved (+4.9 ± 1.9 au, p = 0.01) and SBP tended to improve (‐4.0 ± 2.0 mmHg; p = 0.05) in the ACE+ exercise group only. DBP did not change in any group (p = 0.43). There were significant inverse associations between changes in pathways and SBP (ρ = ‐0.43, p= 0.02) and pathways and ET‐1 (ρ = ‐0.56, p= 0.003), and a significant direct association between changes in SBP and ET‐1 (ρ = 0.49; p = 0.01) in the ACE+ young women. Associations among resilience and BP and ET‐1 were weaker and non‐significant (ρ = ‐0.17–0.29, p≥ 0.13). Our results suggest that structured, progressive exercise training promotes improvements in positive psychological factors, SBP, and circulating ET‐1 levels in young adults with a history of ACEs. Further, changes in pathways were related to changes in SBP and ET‐1 across the intervention period, suggesting a potential psychophysiological relationship between positive psychological traits and cardiovascular risk factors in young women with ACEs.

We investigated the effects of different antihypertensive drugs on the ambulatory arterial stiffness index (AASI), pulse pressure (PP), the arterio-ventricular coupling index (AVCI) and aortic pulse wave velocity (aPWV). After a 4-week placebo period, 94 and 107 patients with uncomplicated hypertension were randomly assigned to treatment with atenolol (AT) at dosage of 50 mg per day or perindopril/indapamide (PER/IND) at dosage of 2/0.6 mg per day for 1 year. From each patient's 24-h ambulatory blood pressure (BP) recording, we determined the 24-h systolic and diastolic BPs. We computed PP as the difference between 24-h systolic and diastolic BP, AASI as unity minus the regression slope of diastolic on systolic BP, and AVCI as (T/τ)/(1+2T/3τ), where T is the heart period in seconds and τ is the decay time of aortic BP during diastole. On AT compared with PER/IND, with adjustments applied for covariables, 24-h systolic BP (-9.5 vs. -13.7 mm Hg; P=0.009) and 24-h PP (-1.02 vs. -6.53 mm Hg; P<0.001) decreased less and AVCI lengthened more (+0.019 vs. -0.008; P<0.001). The changes in AASI (-0.001 vs. -0.014; P=0.44) and aPWV (-0.89 vs. -0.69 m s(-1); P=0.45) were similar in the two treatment groups. AASI and aPWV showed significant concordance (r=0.21, P=0.003) after adjustment for covariables. On administration of antihypertensive drugs with different hemodynamic profiles, AASI and aPWV behaved similarly. The similarity in the findings for aPWV and AASI support the use of AASI as an index reflecting the arterial stiffness.

Gastrodin, a bioactive component in Gastrodina elata Bl., has been approved as a drug for the treatment for dizziness and headache in China 1. Combined with antihypertensive drugs, gastrodin was employed to deal with refractory hypertension in the elderly, but the effect of gastrodin alone on hypertension remains unknown. Arterial baroreflex plays a crucial role in the regulation of cardiovascular activities, and baroreflex function impairment should be regarded as an independent risk factor in hypertension. A new strategy, improving the impaired arterial baroreflex function, has been promoted to treat cardiovascular disease 2. Glutamate (GLU) and gamma-amino butyric acid (GABA), the most common neurotransmitters in the central nerve system (CNS), were both involved in baroreflex regulation 3. Our present experiment was designed to investigate the effect of gastrodin on hypertension, baroreflex sensitivity (BRS) and content of GLU and GABA in the CNS in spontaneously hypertensive rat (SHR). Spontaneously hypertensive rat (20–22 weeks of age) received gastrodin (Xi'nan Co., Chongqing, China) via the left femoral vein in doses of 8, 80 and 800 mg/kg (n = 7 per group). Blood pressure, heart period (HP) and BRS were recorded 0.5 h before and 2 h after drug administration in conscious freely moving SHR 4. It was found that BRS was significantly enhanced after administration in 80 and 800 mg/kg (Figure 1D), while no significant difference was found (Figure 1A–C) in systolic blood pressure, diastolic blood pressure and HP. In another experiment, 2 h after bolus injection of gastrodin (80 or 800mg/kg, ip) or vehicle (n = 7–9 per group), content of GLU and GABA in whole brain of SHR was determined 4 using HPLC/MS. Gastrodin increased GABA content significantly in 800 mg/kg group (Figure 2A). No similar results were found about GLU content (Figure 2B). The present study has directly demonstrated for the limited times that, independent of blood pressure reduction, gastrodin can significantly improve baroreflex function. The blood pressure was not the unique but the most common factor that influence arterial baroreflex. When a drug lowers blood pressure, BRS often increased. Gastrodin, similar to low dose of ketanserin 5, was one of the few drugs that can enhance BRS, not attributable to the normalization of BP levels. As baroreflex was an independent factor that causes end-organs damage in hypertension 2, the study of baroreflex mechanism became more and more important. The effect of gastrodin improving baroreflex without reducing blood pressure may help investigating baroreflex mechanism from more directions than blood pressure reduction. Common mechanism of blood pressure and baroreflex in the CNS, especially in the nucleus of the solitary tract (NTS), was well reported 6, 7. GABA regulated both blood pressure and baroreflex in the NTS, and injection of GABA agonists within the NTS produced an inhibition of NTS neurons, which resulted in reduction in the baroreflex bradycardia and an increase in arterial pressure 6. Meanwhile, GLU receptor antagonists block arterial baroreflex as well as regulate blood pressure in the NTS or in the caudal ventrolateral medulla 8. Gastrodin decreased immunoreactivities of GABA shunt enzymes in the hippocampus 9 and ameliorated the cerebral injury in the rats of cerebral ischaemia reperfusion by improving the level of GABA in striatum 10. Our present study indicated gastrodin increased GABA content in the CNS. All these evidence suggested that GABA increased as a secondary effect in the CNS owing to the gastrodin administration. In summary, gastrodin improved BRS without decreasing blood pressure in SHR. The study was supported by Sciences and Technology Developing Plan grant (No. 2008GG2NS02006) of Shandong Province, and the authors appreciate expert technical assistances from the Second Military Medical University and the Academy of Military Medical Sciences. The authors declare no conflict of interest.

Blood pressure regulation in women – differences emerge when challenged by orthostasis

The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBRS with the sequence technique in healthy male subjects during passive head-up tilt test (HUTT, n = 58), during supine wakefulness, supine slow-wave sleep (SWS), and in the seated and active standing positions (n = 8), and during progressive loss of 1 L blood (n = 8) to decrease central venous pressure in the supine position. HUTT, SWS, the seated, and the standing positions, but not blood loss, entailed significant increases in the positive correlation between HP and the previous SAP values, which is the expected result of arterial baroreflex control, compared with baseline recordings in the supine position during wakefulness. These increases were mirrored by increases in the low-frequency variability of SAP in each condition but SWS. cBRS decreased significantly during HUTT, in the seated and standing positions, and after blood loss compared with baseline during wakefulness. These decreases were mirrored by decreases in the RMSSD index, which reflects cardiac vagal modulation. These results support the view that the cBRS decrease associated with the upright posture is a byproduct of decreased cardiac vagal modulation, triggered by the arterial baroreflex in response to central hypovolemia. Conversely, the greater baroreflex contribution to cardiac control associated with upright posture may be explained, at least in part, by enhanced fluctuations of SAP, which elicit a more effective entrainment of HP fluctuations by the arterial baroreflex. These SAP fluctuations may result from enhanced fluctuations of vascular resistance specific to the upright posture, and not be driven by the accompanying central hypovolemia.

Postural blood pressure differences in pregnancy: A prospective study of blood pressure differences between supine and left lateral position as measured by ultrasound

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

We propose a simple moving-average (MA) model that uses the low-frequency (LF) component of the peroneal muscle sympathetic nerve spike rate (LF(spike rate)) and the high-frequency (HF) component of respiration (HF(Resp)) to describe the LF neurovascular fluctuations and the HF mechanical oscillations in systolic blood pressure (SBP), respectively. This method was validated by data from eight healthy subjects (23-47 yr old, 6 male, 2 female) during a graded tilt (15 degrees increments every 5 min to a 60 degrees angle). The LF component of SBP (LF(SBP)) had a strong baroreflex-mediated feedback correlation with LF(spike rate) (r = -0.69 +/- 0.05) and also a strong feedforward relation to LF(spike rate) [r = 0.58 +/- 0.03 with LF(SBP) delay (tau) = 5.625 +/- 0.15 s]. The HF components of spike rate (HF(spike rate)) and SBP (HF(SBP)) were not significantly correlated. Conversely, HF(Resp) and HF(SBP) were highly correlated (r = -0.79 +/- 0.04), whereas LF(Resp) and LF(SBP) were significantly less correlated (r = 0.45 +/- 0.08). The mean correlation coefficients between the measured and model-predicted LF(SBP) (r = 0.74 +/- 0.03) in the supine position did not change significantly during tilt. The mean correlation between the measured and model-predicted HF(SBP) was 0.89 +/- 0.02 in the supine position. R(2) values for the regression analysis of the model-predicted and measured LF and HF powers indicate that 78 and 91% of the variability in power can be explained by the linear relation of LF(spike rate) to LF(SBP) and HF(Resp) to HF(SBP). We report a simple two-component model using neural sympathetic and mechanical respiratory inputs that can explain the majority of blood pressure fluctuation at rest and during orthostatic stress in healthy subjects.

In early studies of humans, baroreflex sensitivity was found to be higher during sleep; however, subsequent observations in several species, including humans, have been at variance with the original reports. Sleep and arousal are behavioral states, and it is difficult to accurately and repeatedly measure baroreflex sensitivity in behaving animals. However, pharmacologically immobilized (neuromuscularly blocked) rats have apparently normal sleep-wakefulness cycles, and baroreflex gain can be measured directly in this preparation. Using the delta band of the EEG (EEG(delta)) as an index of sleep and arousal and open-loop aortic depressor nerve (ADN) stimulation as a baroreflex input, we found that blood pressure (BP) level depended on arousal (r = -0.416; P < 0.0001), and BP baroreflex gain depended on BP level (r = 0.496; P < 0.0001), but that BP baroreflex gain was independent of arousal (r = 0.001; NS). Heart period (HP) was different; although HP level depended on arousal (r = 0.352; P < 0.0001), HP baroreflex gain did not depend on HP level (r = 0.029; NS), and HP baroreflex gain increased with arousal (r = 0.315; P < 0.0001). A partial-correlations analysis showed that the presence of the relationship between BP level and BP baroreflex gain probably attenuated the relationship between arousal and BP gain. The results are consistent 1) with physiological findings showing that arousal attenuates afferent transmission through the nucleus of the solitary tract and enhances sympathoinhibition at the rostral ventrolateral medulla; and 2) with observations in humans and animals showing increased cardiac baroreflex sensitivity during sleep, but little if any effect of sleep on BP baroreflex sensitivity. The findings are relevant to all methods of baroreflex gain estimation that use HP as the index of baroreflex activation.

### Case A 68-year-old right-hand-dominant man was brought to the hospital because of a speech disturbance and right arm and leg weakness. He awoke with these deficits and was last known to be symptom-free when retiring to bed the previous evening 8 hours earlier. His past medical history was notable for coronary heart disease, the patient having underwent coronary artery bypass surgery 7 years previously for unstable angina, but he had no known history of myocardial infarction. He also had hypertension and hyperlipidemia, and smoked 1 pack of cigarettes daily for more than 40 years. He had no history of calf claudication. His hypertension was being treated with a diuretic and β-adrenergic receptor blocker. He was also prescribed 325 mg of aspirin daily and an HMG CoA-reductase inhibitor (statin); however, his wife remarked that he often forgot to take his medications. His last total cholesterol was 240 mg/dL, with LDL cholesterol of 130 mg/dL. He had a strong family history of coronary heart disease after the age of 50. He had no known drug allergies. #### Physical Examination The patient’s blood pressure was 195/100 mm Hg in both arms, with a regular pulse of 90 bpm. His weight was 225 lb (body mass index: 31.4 kg/m2). His lungs were clear to auscultation. Cardiac examination showed a laterally displaced point of maximum impulse with an S4 gallop and a soft nonradiating systolic murmur at the base. His abdomen was obese without organomegaly and no abdominal bruits were detected. He had no rashes and no joint deformities. The left superficial temporal artery pulse was stronger than the right. There were soft bilateral anterior cervical bruits, left louder than right, but no supraclavicular bruits. There were bilateral femoral bruits. Radial pulses were 2+ and symmetric. Dorsalis pedis and posterior tibial pulses were 1+. …