Can Plasma Volume Determination in Cirrhosis Be Replaced by an Algorithm Using Body Weight and Hematocrit?

BACKGROUND: Patients with cirrhosis often develop hyperdynamic circulation with increased cardiac output, heart rate, and redistribution of the circulating volume with expanded plasma volume (PV). PV determination is part of the evaluation of patients with cirrhosis, but gold-standard methods are invasive, expensive, and time-consuming. Therefore, other estimations of PV would be preferable, and the aim of this study was therefore to study if PV, as assessed by a simplified algorithm based on hematocrit and weight, can replace the gold-standard method. METHODS: We included 328 patients with cirrhosis who had their PV assessed by the indicator dilution technique as the gold-standard method (PVI-125). Actual PV was estimated as PVa = (1 - hematocrit)·(a + (b·body weight)). Ideal PV was estimated as PVi = c · body weight, where a, b, and c are constants. RESULTS: PVI-125, PVa, and PVi were 3.99 ± 1.01, 3.09 ± 0.54, and 3.01 ± 0.65 (Mean ± SD), respectively. Although PVI-125 correlated significantly with PVa (r = 0.72, p < 0.001), a Bland-Altman plot revealed wide limits of confidence. CONCLUSIONS: The use of simplified algorithms does not sufficiently estimate PV and cannot replace the indicator dilution technique.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.

Estimated glomerular filtration rate based on creatinine, cystatin C, ß-trace protein and ß2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

AIMS: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, ß-trace protein (BTP) and ß2 microglobulin (B2M) among patients undergoing major amputation. METHODS: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. RESULTS: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. CONCLUSION: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Evaluation of Multi-Frequency Bioelectrical Impedance Analysis against Dual-Energy X-ray Absorptiometry for Estimation of Low Muscle Mass in Older Hospitalized Patients.

The accuracy of multi-frequency (MF) bioelectrical impedance analysis (BIA) to estimate low muscle mass in older hospitalized patients remains unclear. This study aimed to describe the ability of MF-BIA to identify low muscle mass as proposed by The Global Leadership Initiative on Malnutrition (GLIM) and The European Working Group on Sarcopenia in Older People (EWGSOP-2) and examine the association between muscle mass, dehydration, malnutrition, and poor appetite in older hospitalized patients. In this prospective exploratory cohort study, low muscle mass was estimated with MF-BIA against dual-energy X-ray absorptiometry (DXA) in 42 older hospitalized adults (≥65 years). The primary variable for muscle mass was appendicular skeletal muscle mass (ASM), and secondary variables were appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI). Cut-off values for low muscle mass were based on recommendations by GLIM and EWGSOP-2. MF-BIA was evaluated against DXA on the ability to estimate absolute values of muscle mass by mean bias, limits of agreement (LOA), and accuracy (5% and 10% levels). Agreement between MF-BIA and DXA to identify low muscle mass was evaluated with sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The association between muscle mass, dehydration, malnutrition, and poor appetite was visually examined with boxplots. MF-BIA overestimated absolute values of ASM with a mean bias of 0.63 kg (CI: -0.20:1.46, LOA: -4.61:5.87). Agreement between MF-BIA and DXA measures of ASM showed a sensitivity of 86%, specificity of 94%, PPV of 75% and NPV of 97%. Boxplots indicate that ASM is lower in patients with malnutrition. This was not observed in patients with poor appetite. We observed a tendency toward higher ASM in patients with dehydration. Estimation of absolute ASM values with MF-BIA should be interpreted with caution, but MF-BIA might identify low muscle mass in older hospitalized patients.

Gastric Emptying Is Not Delayed and Does Not Correlate With Attenuated Postprandial Blood Flow Increase in Medicated Patients With Early Parkinson's Disease.

Background: We have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls. Objective: To investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying. Methods: We studied 15 patients with PD in an "ON-medication" state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA. Results: The dynamics of gastric emptying did not differ between groups (p = 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously (p = 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA. Conclusion: Our preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying.

Optimization of Nutrition And Medication (OptiNAM) for acutely admitted older patients: protocol for a randomized single-blinded controlled trial.

BACKGROUND: Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on 99mTechnetium-diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED. METHODS: The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge. DISCUSSION: The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED. TRAIL REGISTRATION: ClinicalTrials.gov NTC03741283 . Retrospectively registered on 14 November 2018.

Gastrointestinal motility, gut hormone secretion, and energy intake after oral loads of free fatty acid or triglyceride in older and middle-aged men.

In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ±â€¯3.4 (mean ±â€¯SD) years) and 10 middle-aged (age 43.1 ±â€¯8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p < 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p < 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p < 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.

Relationship between Sodium Intake and Water Intake: The False and the True.

BACKGROUND: Generally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial. The purpose of this review is to provide examples of how the kidney handles water in relation to salt intake/output. It is based on re-analysis of previously published studies in which salt intake was adjusted to several different levels in the same subjects, and in databases of epidemiologic studies in populations on an ad libitum diet. Summary and Key Messages: These re-analyses allow us to draw the following conclusions: (1) In a steady state situation, the urine volume (and thus the fluid intake) remains unchanged over a large range of sodium intakes. The adaptation to a higher sodium excretion rests only on changes in urinary sodium concentration. However, above a certain limit, this concentration cannot increase further and the urine volume may then increase. (2) In population studies, it is not legitimate to assume that sodium is responsible for changes in urine volume, since people who eat more sodium also eat more of other nutrients leading to an increase in the excretion of potassium, urea and other solutes, besides sodium. (3) After an abrupt increase in sodium intake, fluid intake is increased in the first few days, but urine volume does not change. The extra fluid drunk is responsible for an increase in body weight.

Hemodynamic responses to mental stress during salt loading.

PURPOSE: The purpose was to examine whether prolonged moderate stress associated with a student exam would increase the blood pressure response to a salt load in young healthy normotensive individuals. METHODS: Ten healthy young subjects were examined at two different occasions in random order (i) during preparation for a medical exam (prolonged stress) and (ii) outside the exam period (low stress). All subjects consumed a controlled diet for 3 days with low- or high-salt content in randomized order. The subjective stress was measured by Spielberger's State-Trait Anxiety Inventory-Scale, SCL Symptom Checklist for stress and the Visual Analogue Scale. On each level of stress, 24-h ambulatory blood pressure and cardiac output (CO) were measured. Furthermore, plasma norepinephrine (NE), epinephrine (E) and plasma renin activity (PRA) were measured. RESULTS: Twenty-four-hour ABP, 24-h heart rate, CO as well as plasma levels of NE, E and PRA remained unchanged by changes in stress level. Day-night reduction in SAP was significantly larger during moderate stress and high-salt intake; however, no significant difference was observed during daytime and night-time. Individual increase in mental stress correlated significantly with an individual decrease in PRA (SCL-17, r = -0·80, P<0·05, STAIr = -0·64 P<0·05) during high-salt intake. CONCLUSION: Moderate stress over a period of time in young healthy normotensive individuals does not lead to changes in 24-h ABP. However, the augmented reduction in day-to-night systolic blood pressure during high-salt intake and moderate stress may indicate that stress affects blood pressure regulation.

Early 24-hour blood pressure response to Roux-en-Y gastric bypass in obese patients.

Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean BMI 40.8 kg/m2) and 10 severely obese normotensive (mean BMI 41.7 kg/m2) patients underwent 24-h ambulatory blood pressure measurements (24 h ABPMs) before LRYGB and again day 1 and day 10 after LRYGB. No change in 24 h BP was observed day 1 after LRYGB. Day 10 after surgery both hypertensive and normotensive patients demonstrated a significant 12.6 mmHg and 9.5 reduction in systolic BP (SBP), respectively. Mean arterial pressure (MAP) decreased by 8.3 and 5.4 mmHg. At day 10 postoperatively, a weight loss of 7.9 kg in the hypertensive patients and 7.0 kg in the normotensive patients was observed. The reduction in BP after LRYGB takes place before any substantial weight loss has occurred. The reason for this remains speculative, but obese hypertensive patients may clearly benefit from the operation even if the goal of achieving 'normoweight' is not obtained.

Diagnosis of bile acid diarrhoea by fasting and postprandial measurements of fibroblast growth factor 19.

BACKGROUND: A deficiency in the ileal hormone fibroblast growth factor 19 (FGF19) has been described in patients with bile acid diarrhoea (BAD), but fasting FGF19 levels have insufficient diagnostic power. We assess whether single postprandial sampling of FGF19 has greater discriminative value than fasting FGF19 for detection of BAD and we evaluate the reproducibility of fasting FGF19. MATERIALS AND METHODS: Twenty-six patients consecutively referred to Se homocholic acid retention test (SeHCAT) were included. Serum FGF19 was measured after an overnight fast and again 1 h postprandially and again in the fasting state 1 week later. RESULTS: Nine of 26 patients had SeHCAT less than 10% and fasting FGF19 was lower [median 62 pg/ml, interquartile range (IQR): 47-67] than in the 17 diarrhoea controls with SeHCAT at least 10% (median 103 pg/ml, IQR: 77-135, P=0.006). Postprandial FGF19 in BAD patients (61 pg/ml, IQR: 48-69) was similar to fasting values (P=0.59) and increased insignificantly in diarrhoea controls (137 pg/ml, IQR: 88-182; P=0.25). The difference in postprandial FGF19 between patients with BAD and diarrhoea controls was highly significant (P<0.001). CONCLUSION: The difference in serum FGF19 between groups of patients with BAD and diarrhoea controls is amplified postprandially. Within each group, the difference between fasting and postprandial FGF19 was not statistically significant. Further investigations are warranted on stimulated FGF19 response to elucidate its role in BAD.

Absorption and initial metabolism of 75Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data.

Selenomethionine (SeMet) is an important organic nutritional source of Se, but the uptake and metabolism of SeMet are poorly characterised in humans. Dynamic gamma camera images of the abdominal region were acquired from eight healthy young men after the ingestion of radioactive 75Se-l-SeMet (75Se-SeMet). Scanning started simultaneously to the ingestion of 75Se-SeMet and lasted 120 min. We generated time-activity curves from two-dimensional regions of interest in the stomach, small intestine and liver. During scanning, blood samples were collected at 10-min intervals to generate plasma time-activity curves. A four-compartment model, augmented with a delay between the liver and plasma, was fitted to individual participants' data. The mean rate constant for 75Se-SeMet transport was 2·63 h-1 from the stomach to the small intestine, 13·2 h-1 from the small intestine to the liver, 0·261 h-1 from the liver to the plasma and 0·267 h-1 from the stomach to the plasma. The delay in the liver was 0·714 h. Gamma camera imaging provides data for use in compartmental modelling of 75Se-SeMet absorption and metabolism in humans. In clinical settings, the obtained rate constants and the delay in the liver may be useful variables for quantifying reduced intestinal absorption capacity or liver function.

Body height and arterial pressure in seated and supine young males during +2 G centrifugation.

It is known that arterial pressure correlates positively with body height in males, and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore, we tested the hypothesis that a higher gravito-inertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162-171 cm; n = 8) and tall (194-203 cm; n = 10) healthy males (18-41 yr), brachial arterial pressure, heart rate (HR), and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22 ± 2 mmHg, P < 0.0001) and tall (23 ± 2 mmHg, P < 0.0001) males, with no significant difference between the groups. HR increased more (P < 0.05) in the tall than in the short group (14 ± 2 vs. 7 ± 2 bpm). Stroke volume (SV) decreased in the short group (26 ± 4 ml, P = 0.001) and more so in the tall group (39 ± 5 ml, P < 0.0001; short vs. tall, P = 0.047). During +2Gx, systolic arterial pressure increased (P < 0.001) and SV (P = 0.012) decreased in the tall group only. In conclusion, during +2Gz, MAP increased in both short and tall males, with no difference between the groups. However, in the tall group, HR increased more during +2Gz, which could be caused by a larger hydrostatic pressure gradient from heart to head, leading to greater inhibition of the carotid baroreceptors.

Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight.

KEY POINTS: Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure.It is unclear whether these changes persist throughout months of flight.Here, we show that cardiac output and stroke volume increase by 35­41% between 3 and 6 months on the International Space Station, which is more than during shorter flights.Twenty-four hour ambulatory brachial blood pressure is reduced by 8­10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space.It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station. ABSTRACT: Acute weightlessness in space induces a fluid shift leading to central volume expansion. Simultaneously, blood pressure is either unchanged or decreased slightly. Whether these effects persist for months in space is unclear. Twenty-four hour ambulatory brachial arterial pressures were automatically recorded at 1­2 h intervals with portable equipment in eight male astronauts: once before launch, once between 85 and 192 days in space on the International Space Station and, finally, once at least 2 months after flight. During the same 24 h, cardiac output (rebreathing method) was measured two to five times (on the ground seated), and venous blood was sampled once (also seated on the ground) for determination of plasma catecholamine concentrations. The 24 h average systolic, diastolic and mean arterial pressures (mean ± se) in space were reduced by 8 ± 2 mmHg (P = 0.01; ANOVA), 9 ± 2 mmHg (P < 0.001) and 10 ± 3 mmHg (P = 0.006), respectively. The nightly blood pressure dip of 8 ± 3 mmHg (P = 0.015) was maintained. Cardiac stroke volume and output increased by 35 ± 10% and 41 ± 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged; and systemic vascular resistance was reduced by 39 ± 4% (P < 0.001). The increase in cardiac stroke volume and output is more than previously observed during short duration flights and might be a precipitator for some of the vision problems encountered by the astronauts. The spaceflight vasodilatation mechanism needs to be explored further.

Roux-en-Y gastric bypass alleviates hypertension and is associated with an increase in mid-regional pro-atrial natriuretic peptide in morbid obese patients.

OBJECTIVE: To examine 24-h blood pressure (24BP), systemic haemodynamics and the effect of sodium intake on 24BP in obese patients before and after gastric bypass surgery [laparoscopic Roux-en-Y gastric bypass (LRYGB)], and to determine whether weight loss from LRYGB might be related to an increase in plasma concentrations of atrial natriuretic peptide. METHODS: Twelve hypertensive and 12 normotensive morbidly obese patients underwent LRYGB: 24BP, systemic haemodynamics and mid-regional pro-atrial natriuretic peptide (MRproANP) were assessed before, 6 weeks and 12 months after surgery. The effect of high versus low sodium intake on 24BP was evaluated before and 12 months after LRYGB. RESULTS: Six weeks after LRYGB, the average weight loss was 20 kg, with a further 21 kg weight loss 1 year after surgery. In hypertensive patients, 24BP was significantly reduced at 6 weeks, but not 1 year after LRYGB. However, antihypertensive medications were successively reduced from baseline to 1 year after surgery. In normotensive patients, there was no change in 24BP 6 weeks after LRYGB, but a tendency towards a reduction 1 year after the operation. Plasma concentrations of MRproANP were subnormal prior to surgery in hypertensive patients and increased by 77% 1 year after the operation. In normotensive patients, preoperative concentrations were normal and increased only by 6%. High sodium intake induced plasma volume expansion, increased stroke volume and cardiac output, but no significant change in 24BP - neither before nor after LRYGB. CONCLUSIONS: LRYGB resulted in a significant 24BP reduction and a substantial increase in MRproANP plasma concentrations in hypertensive, obese patients 6 weeks after surgery, suggesting a causal link between obesity-hypertension and altered release/degradation of cardiac natriuretic peptides.

Calculated plasma volume status and prognosis in chronic heart failure.

AIMS: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. METHODS AND RESULTS: First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2) = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. CONCLUSIONS: Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.