J.W.M. Lenders

Both body and arm position significantly influence blood pressure measurement

The position of both the body and the arm during indirect blood pressure (BP) measurement is often neglected. The aim of the present study was to test the influence of the position of the patient on BP readings: (1) sitting with the arms supported precisely at the right atrium level and (2) supine: (a) with the arms precisely at the right atrium level and (b) with the arms on the examination bed. In a first group of 57 hypertensive patients, two sessions of BP and heart rate (HR) measurements were performed in two positions: sitting and supine with the arms supported precisely at right atrium level in both positions. BP was measured simultaneously at both arms, with a Hawksley Random Zero sphygmomanometer at the right arm, and with an automated oscillometric device (Bosomat) at the left arm. BP and HR readings obtained in the two positions were then compared. In a second group of 25 normo- and hypertensive persons, two sessions of BP and HR readings were performed in supine with the arms in two different arm positions: (a) the arm placed precisely at right atrium level and (b) the other arm on the examination bed. The measurements were performed at both arms with two automated devices (Bosomat). The readings taken in the two positions were compared. Both systolic BP (SBP; by 9.5±9.0 (standard deviation, s.d.); right arm) and diastolic BP (DBP; by 4.8±6.0 mmHg; right arm) were significantly higher in the supine than in the sitting position. When the two different arm positions (body continously supine) were compared in the second part of the study, significantly higher SBP (by 4.6±6.1 mmHg) and DBP (by 3.9±2.8 mmHg) were obtained when the arm of the patient was placed on the bed (below the right atrium level), than when the arm was placed at the level of the right atrium. BP readings in sitting and supine positions are not the same. When according to guidelines the arm of the patient is meticulously placed at the right atrium level in both positions, the difference is even greater than when the arm rests on the desk or on the arm support of the chair. Moreover, in the supine position small but significant differences in BP are measured between arm on a 5 cm-high pillow and arm on the bed. In every study reporting BP values, the position of both the body and especially the arm should be precisely mentioned.

Adrenal nodularity and somatic mutations in primary aldosteronism: One node is the culprit?

CONTEXT Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. OBJECTIVE The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. DESIGN AND METHODS We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. RESULTS Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. CONCLUSIONS Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.

Autonomic function in patients with chronic fatigue syndrome

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4±10.5 beats) than in healthy controls (32.2±9.5) (p=0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6±8.9 beats) and the control group (40.2±8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6±9.9) than in the control group (29.5±16.7) (p<0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.

Arm position is important for blood pressure measurement

Aim: To test the effect of positioning the arm on the arm-rest of a common chair, below the officially recommended right atrial level, on the blood pressure (BP) readings in a group of out-patients.Patients and methods: A group of 69 patients (58 hypertensives; 39 males; mean ± s.d. age 54.1 ± 16.0 years) participated in the present study. BP and heart rate values obtained in each of the following two positions were compared: (1) sitting with the arms supported on the arm-rests of the chair and (2) sitting with the arms supported at the level of the mid-sternum (the approximation of the right atrial level). BP was measured simultaneously at both arms, with a mercury sphygmomanometer at the right arm and with an automatic oscillometric device at the left arm.Results: Both the systolic and diastolic BPs were significantly higher (P < 0.0001) when the arm was placed on the arm-rest of the chair than at the right atrial level. the same differences ± s.d. in bp between the two positions were obtained with both measurement techniques: 9.7 ± 9.4 mm hg (systolic) and 10.8 ± 5.8 mm hg (diastolic) with the mercury sphygmomanometer and respectively 7.3 ± 8.9 mm hg and 8.3 ± 6.0 mm hg with the oscillometric device. no difference in the heart rate was found between the two positions.Conclusions: Placing the patient’s arms on the arm-rest of the chair instead of at the reference right atrial level, BP measurement will result in spuriously elevated BP values. This may be of great importance for the diagnosis and the subsequent treatment decisions for patients with hypertension.

Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome.

Abstract.Background: Data on the prevalence of orthostatic intolerance (OI) in patients with chronic fatigue syndrome (CFS) are limited and controversial. We tested the hypothesis that a majority of CFS patients exhibit OI during head-up tilt. Methods: Hemodynamic and neurohumoral responses to 40 minutes of head-up tilt were studied in 36 CFS patients and 36 healthy controls. Changes in stroke volume, cardiac output and peripheral vascular resistance were estimated from finger arterial pressure waveform analysis (Modelflow). Blood samples were drawn before and at the end of head-up tilt for measurement of plasma catecholamines. Results: At baseline, supine heart rate was higher in CFS patients (CFS: 66.4 ± 8.4 bpm; controls: 57.4 ± 6.6 bpm; p < 0.001) as was the plasma epinephrine level (CFS: 0.11 ± 0.07 nmol/l; controls: 0.08 ± 0.07 nmol/l: p = 0.015). An abnormal blood pressure and/or heart rate response to head-up tilt was seen in 10 (27.8 %) CFS patients (6 presyncope, 2 postural tachycardia, 2 tachycardia and presyncope) and 6 (16.7 %, p = 0.26) controls (5 presyncope, 1 tachycardia, 2 tachycardia and presyncope). Head-up tilt-negative CFS patients showed a larger decrease in stroke volume during tilt (−46.9 ± 10.6) than head-up tilt-negative controls (−40.3 ± 13.6 %, p = 0.008). Plasma catecholamine responses to head-up tilt did not differ between these groups. Conclusion: Head-up tilt evokes postural tachycardia or (pre)syncope in a minority of CFS patients. The observations in head-up tilt-negative CFS patients of a higher heart rate at baseline together with a marked decrease in stroke volume in response to head-up tilt may point to deconditioning.

Correlation Between In Vivo 18F-FDG PET and Immunohistochemical Markers of Glucose Uptake and Metabolism in Pheochromocytoma and Paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) can be localized by 18F-FDG PET. The uptake is particularly high in tumors with an underlying succinate dehydrogenase (SDH) mutation. SDHx-related PPGLs are characterized by compromised oxidative phosphorylation and a pseudohypoxic response, which mediates an increase in aerobic glycolysis, also known as the Warburg effect. The aim of this study was to explore the hypothesis that increased uptake of 18F-FDG in SDHx-related PPGLs is reflective of increased glycolytic activity and is correlated with expression of different proteins involved in glucose uptake and metabolism through the glycolytic pathway. Methods: Twenty-seven PPGLs collected from patients with hereditary mutations in SDHB (n = 2), SDHD (n = 3), RET (n = 5), neurofibromatosis 1 (n = 1), and myc-associated factor X (n = 1) and sporadic patients (n = 15) were investigated. Preoperative 18F-FDG PET/CT studies were analyzed; mean and maximum standardized uptake values (SUVs) in manually drawn regions of interest were calculated. The expression of proteins involved in glucose uptake (glucose transporters types 1 and 3 [GLUT-1 and -3, respectively]), phosphorylation (hexokinases 1, 2, and 3 [HK-1, -2, and -3, respectively]), glycolysis (monocarboxylate transporter type 4 [MCT-4]), and angiogenesis (vascular endothelial growth factor [VEGF], CD34) were examined in paraffin-embedded tumor tissues using immunohistochemical staining with peroxidase-catalyzed polymerization of diaminobenzidine as a read-out. The expression was correlated with corresponding SUVs. Results: Both maximum and mean SUVs for SDHx-related tumors were significantly higher than those for sporadic and other hereditary tumors (P < 0.01). The expression of HK-2 and HK-3 was significantly higher in SDHx-related PPGLs than in sporadic PPGLs (P = 0.022 and 0.025, respectively). The expression of HK-2 and VEGF was significantly higher in SDHx-related PPGLs than in other hereditary PPGLs (P = 0.039 and 0.008, respectively). No statistical differences in the expression were observed for GLUT-1, GLUT-3, and MCT-4. The percentage anti-CD 34 staining and mean vessel perimeter were significantly higher in SDHx-related PPGLs than in sporadic tumors (P = 0.050 and 0.010, respectively). Mean SUVs significantly correlated with the expression of HK-2 (P = 0.027), HK-3 (P = 0.013), VEGF (P = 0.049), and MCT-4 (P = 0.020). Conclusion: The activation of aerobic glycolysis in SDHx-related PPGLs is associated with increased 18F-FDG accumulation due to accelerated glucose phosphorylation by hexokinases rather than increased expression of glucose transporters.

Influence of the arm position on intra- arterial blood pressure measurement

The reference level for the measurement of blood pressure (BP) is the level of the right atrium. In practice this is regularly disregarded, as the patient’s arm is usually placed lower than the right atrial level. The aim of the study was to determine the influence of first, different arm positions and second, different transducer positions on the intra-arterially (i.a.) recorded BP. In 16 healthy men (age 28.1 ± 8.0 (s.d.) years), i.a. BP was recorded at the left arm in supine position, using a 5–7 cm long cannula. The baseline position was with the tip of the cannula placed precisely at the level of the right atrium. Subsequently, the following changes were made: 5, 10, 15 and 20 cm above and 5, 10, 15, and 20 cm below the baseline position. A 2-min rest period was allowed in each position before the BP was measured. The whole procedure was done either with the transducer connected to the arm at the place of the cannula (n = 7), or with the transducer placed next to the subject and continuously kept at the right atrial level during the BP measurement (n = 9). Simultaneously, baseline BP was measured indirectly, with a standard mercury sphygmomanometer, in the opposite arm maintained with the cubital fossa at the right atrial level during the whole procedure. This resulted in the first group of seven volunteers for both the i.a. systolic (SBP) and diastolic BP (DBP) values to significantly decrease (P < 0.001) when the arm together with the transducer were elevated above the level of the right atrium, and returned to the initial value when the arm and the transducer were placed back at the right atrial level. intra-arterial sbp and dbp significantly (P < 0.001) increased as the arm, together with the transducer, were lowered below the right atrial level and returned to the initial value when the arm and the transducer were placed back at the right atrial level. in both directions, each 5 cm change in the arm level was accompanied by a 3–4 mm hg change in the i.a. bp value. the baseline bp, measured sphygmomanometrically at the contralateral arm, remained constant during the whole duration of the procedure. the changes in the i.a. bp were minimal in the second group of nine subjects in which only the arm but not the transducer was placed at different levels. we conclude that small deviations in arm position above or below the ‘gold standard’, ie, the fossa cubiti at the right atrial level, will result in largely erroneous bp values. the correct positioning of the arm during bp measurement is therefore mandatory for the diagnosis and follow-up of hypertensive subjects.

Neurohumoral antecedents of vasodepressor reactions

Abstract. Vasodepressor (vasovagal) syncope, the most common cause of acute loss of consciousness, can occur in otherwise vigorously healthy people during exposure to stimuli decreasing cardiac filling. Antecedent physiological or neuroendocrine conditions for this dramatic syndrome are poorly understood. This study compared neurocirculatory responses to non‐hypotensive lower body negative pressure (LBNP) in subjects who subsequently developed vasodepressor reactions during hypotensive LBNP with responses in subjects who did not. In 26 healthy subjects, LBNP at ‐15 and ‐40mmHg was applied to inhibit cardiopulmonary and arterial baroreceptors. All the subjects tolerated 30min of LBNP at ‐15 mmHg, but during subsequent LBNP at ‐40 mmHg 11 subjects had vasodepressor reactions, with sudden hypotension, nausea, and dizziness. In these subjects, arterial plasma adrenaline responses to LBNP both at ‐15 and at ‐40 mmHg exceeded those in subjects who did not experience these reactions. In 16 of the 26 subjects, forearm noradrenaline spillover was measured; in the eight subjects with a vasodepressor reaction, mean forearm noradrenaline spillover failed to increase during LBNP at ‐15mmHg (Δ= ‐0.06±(SEM) 0.04pmol min‐1 100mL‐1), whereas in the eight subjects without a vasodepressor reaction, mean forearm noradrenaline spillover increased significantly (Δ=0.31±0.13pmolmin‐1100mL‐1). Plasma levels of β‐endorphin during LBNP at ‐15 mmHg increased in some subjects who subsequently had a vasodepressor reaction during LBNP at ‐40 mmHg. The findings suggest that a neuroendocrine pattern including adre‐nomedullary stimulation, skeletal sympathoinhibition, and release of endogenous opioids can precede vasodepressor syncope.

Influence of different supine body positions on blood pressure: consequences for night blood pressure/dipper-status

Objectives To investigate the influence of different supine body positions on blood pressure measured by an ambulatory device. Design and methods Twenty hypertensive and 20 normotensive subjects of a tertiary hospital outpatient clinic participated. Blood pressure was measured with an ambulatory blood pressure device while lying in the back, left side, right side and abdominal positions. The distance between the antecubital fossa and sternum was measured in all four body positions. An expected blood pressure difference between the arm of measurement and the right atrium (i.e. the midsternum) was calculated for the different body positions. Results When blood pressure was measured in side position at the left arm in hypertensive subjects, the mean systolic and diastolic blood pressure differences (± SD) between the left arm in the lower position and in back position at the same arm were +5/+4 (8/6) mmHg. These differences were −14/−17 (6/4) mmHg for the left arm lying above heart level in side position. Values of the right arm in hypertensives and the measurement at both arms in normotensive subjects yielded similar differences. Conclusions Body and arm position can both significantly influence the ambulatory blood pressure and therefore the day-night difference. This comprises one of the main reasons for the moderate individual reproducibility of the blood pressure fall at night.

Home versus Office blood pressure MEasurements: Reduction of Unnecessary treatment Study: rationale and study design of the HOMERUS trial.

The Home versus Office MEasurements, Reduction of Unnecessary treatment Study (HOMERUS) is a multicentre prospective study, primarily designed to examine in subjects with mild to moderate hypertension whether treatment decisions based on home blood pressure measurements can lead to reduction in the use of antihypertensive drugs and the associated costs, compared to office blood pressure measurements. After inclusion, 360 patients are randomized to two groups. In one group, antihypertensive therapy is based on blood pressure measured in the outpatient clinic: the office pressure (OP) group. In the other group, antihypertensive therapy is based on home blood pressure measurements: the self‐pressure (SP) group. All readings, both in OP and in SP, are obtained with the same validated oscillometric device, the Omron 705 CP. Treatment decisions are taken by an independent physician at the coordinating centre, who is unaware whether the patient belongs to the SP or OP group. Following a standardized treatment schedule, blood pressure is targeted at 120–139 mmHg for systolic and 80–89 mmHg for diastolic pressure. Patients are followed for 1 year. At the start and at the end of the study, ambulatory blood pressure measurements are obtained as a reference. Microalbuminuria and echocardiography are assessed to evaluate the possible development of target organ damage. It is expected that, at the end of the trial, patients in both groups will have the same blood pressure, at the expense of more medication in the OP group. Therefore, a cost‐minimization analysis will be performed first. If short‐term effects appear not to be comparable for OP and SP, a cost‐effectiveness analysis will be performed to assess the value of the SP strategy in comparison to standard practice. In addition, medication compliance is recorded within random subgroups of the SP and OP groups by means of Medication Event Monitoring System (MEMS) V TrackCaps.