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Short term variation in NTproBNP after lifestyle intervention in severe obesity.
Fedele, D, Bicchiega, V, Collo, A, Barutta, F, Pistone, E, Gruden, G, Bruno, G
PloS one. 2017;(7):e0181212
Abstract
AIM: Natriuretic peptides are not only involved in cardiovascular adaption to various conditions, but also in metabolic diseases. We performed this study to assess the effect of a very short time of lifestyle inpatient intervention on NTproBNP values in normotensive subjects with severe obesity and normal cardiac function. METHODS We recruited 14 consecutive obese normotensive subjects with normal cardiac function who were aged 30 years and more and were referred to inpatient rehabilitation in an academic clinic over a two months period. They were examined at baseline and after a 3-weeks program including dietary intervention with hypocaloric diet and assisted personalized physical aerobic and anaerobic activities and compared to age, sex and BMI-matched control subjects under usual care. RESULTS BMI significantly decreased (40.8 ±1.6 vs 42.3 ± 1.6 kg/m2, p <0.0001). Median reduction in body weight was 4.9 kg (interquartile range 2.4-5.2 kg). After diet and exercise-induced weight loss, plasma NTproBNP levels showed an almost two-fold increase, which was statistically significant (28.2 ± 12.3 vs 17.2 ± 13.2 ng/L, p = 0.01), and particularly relevant in the subgroup with NT-proBNP values below median values compared to those with higher values (p = 0.02). No significant variations were found in control subjects (18.0 ± 13.0 vs 16.5 ± 11.2 ng/L, p = 0.18). The lipid profile was significantly ameliorated, and both HbA1c and insulin levels showed a marginally non-significant decrease after treatment. CONCLUSIONS An almost two-fold increase in NTproBNP levels was evident after a very short time period of lifestyle intervention in normotensive severe obese patients without cardiac disease. This finding might have clinical relevance, considering the role of NT-proBNP as risk factor of impaired glucose tolerance.
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The effect of surgical and non-surgical weight loss on N-terminal pro-B-type natriuretic peptide and its relation to obstructive sleep apnea and pulmonary function.
Gabrielsen, AM, Omland, T, Brokner, M, Fredheim, JM, Jordan, J, Lehmann, S, Lund, MB, Hjelmesæth, J, Hofsø, D
BMC research notes. 2016;(1):440
Abstract
BACKGROUND Obesity is a major risk factor for obstructive sleep apnea, impaired pulmonary function and heart failure, but obesity is also associated with paradoxically low levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP). In subjects with severe obesity undergoing weight loss treatment, we assessed the associations between changes in severity of obstructive sleep apnea, pulmonary function and serum NT-proBNP levels. METHODS One-year non-randomized controlled clinical trial. Participants, 69.6 % women, mean (SD) age 44.6 (10.8) years and body mass index (BMI) 45.1 (5.6) kg/m(2), underwent gastric bypass surgery (n = 76) or intensive lifestyle intervention (n = 63), resulting in 30 (8) % and 8 (9) % weight loss, respectively. The reference group included 30 normal weight, healthy, gender and age matched controls. Sleep recordings, arterial blood gases, pulmonary function and blood tests were assessed before and 1 year after the interventions. RESULTS NT-proBNP concentrations increased significantly more after surgery than after lifestyle intervention. The post intervention values in both groups were significantly higher than in a normal weight healthy reference group. In the whole study population changes (∆) in NT-proBNP correlated significantly with changes in both BMI (r = -0.213) and apnea hypopnea index (AHI, r = -0.354). ∆NT-proBNP was, independent of age, gender and ∆BMI, associated with ∆AHI (beta -0.216, p = 0.021). ∆AHI was, independent of ∆BMI, significantly associated with changes in pO2 (beta -0.204), pCO2 (beta 0.199), forced vital capacity (beta -0.168) and forced expiratory volume first second (beta -0.160). CONCLUSIONS Gastric bypass surgery was associated with a greater increase in NT-proBNP concentrations than non-surgical weight loss treatment. Reduced AHI was, independent of weight loss, associated with increased NT-proBNP levels and improved dynamic lung volumes and daytime blood gases. Clinical Trial Registration ClinicalTrials.gov NCT00273104, retrospectively registered Jan 5, 2006 (study start Dec 2005).
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The association between arterial stiffness and fluid status in peritoneal dialysis patients.
Kocyigit, I, Sipahioglu, MH, Orscelik, O, Unal, A, Celik, A, Abbas, SR, Zhu, F, Tokgoz, B, Dogan, A, Oymak, O, et al
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2014;(7):781-90
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Abstract
OBJECTIVES In this study our aim was to evaluate the relationship between degree of fluid status and arterial stiffness measured by pulse wave velocity (PWV) in peritoneal dialysis (PD) patients. Fluid status was determined by different methods including fluid overload measured by bioimpedance (Body Composition Monitor, BCM), calf normalized resistivity (CNR), plasma N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and extracellular to intracellular water ratio (ECW/ICW). METHODS Sixty PD patients were evaluated. They were stratified into normo- and hypervolemic groups according to their fluid overload (FO). CNR was calculated from resistance at 5 kHz using calf bioimpedance spectroscopy. Arterial stiffness was assessed by PWV. Additionally, all patients underwent transthoracic echocardiography and had levels of NT-proBNP measured. RESULTS PWV was higher in the hypervolemic compared to normovolemic patients (9.99 ± 2.4 m/sec vs 7.48 ± 2.3 m/sec, p < 0.001). Hypervolemic patients had higher NT-proBNP levels (3065 ± 981 pg/mL vs 1095 ± 502 pg/mL, p < 0.001), a higher ratio of ECW/ICW; (0.93 ± 0.11 vs 0.81 ± 0.08, p < 0.001) and lower CNR (13.7 ± 2.4 vs 16.0 ± 3.3 W m(3)/kg(*)10(-2), p = 0.005). NT-pro BNP level, ECW/ICW ratio, relative FO, and left ventricular (LV) mass index were positively and CNR negatively correlated with PWV. Relative FO and CNR independently predicted PWV in multivariate analysis adjusted for age, duration of PD, body mass index and mean arterial pressure. CONCLUSIONS Arterial stiffness is increased in fluid-overloaded PD patients. Our results indicated that fluid status is an independent predictor of PWV.
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Leptin increases prostate cancer aggressiveness.
López Fontana, CM, Maselli, ME, Pérez Elizalde, RF, Di Milta Mónaco, NA, Uvilla Recupero, AL, López Laur, JD
Journal of physiology and biochemistry. 2011;(4):531-8
Abstract
Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.
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NT-ProBNP levels, water and sodium homeostasis in healthy men: effects of 7 days of dry immersion.
Navasiolava, NM, Pajot, A, Gallois, Y, Pastushkova, LKh, Kulchitsky, VA, Gauquelin-Koch, G, Kozlovskaya, IB, Heer, M, Hand, O, Larina, IM, et al
European journal of applied physiology. 2011;(9):2229-37
Abstract
Immersion is a useful tool for studying fluid-volume homeostasis. Natriuretic peptides play a vital role in renal, humoral, and cardiovascular regulation under changing environmental conditions. We hypothesized that dry immersion would rapidly induce a new steady state for water and sodium metabolism, and that serum NT-proBNP levels, a proxy measure for brain natriuretic peptide (BNP), would decrease during long-term dry immersion and increase during recovery. Eight healthy young men were studied before, during, and after 7 days of dry immersion. Body weight, water balance, and plasma volume changes were evaluated. Plasma and serum samples were analyzed for active renin, NT-proBNP, aldosterone, electrolytes, osmolality, total protein, and creatinine. Urine samples were analyzed to determine levels of electrolytes, osmolality, creatinine, and free cortisol. A stand test was performed before and after dry immersion to evaluate cardiovascular deconditioning. Long-term dry immersion induced acute changes in water and sodium homeostasis on day 1, followed by a new steady state. Plasma volume decreased significantly during dry immersion. The serum levels of NT-proBNP increased significantly in recovery (10 ± 3 ng/L before dry immersion vs. 26 ± 5 ng/L on the fourth recovery day). Heart rate in the standing position was significantly greater after immersion. Results suggest that chronic dry immersion rapidly induced a new level of water-electrolyte homeostasis. The increase in NT-proBNP levels during the recovery period may be related to greater cardiac work and might reflect the degree of cardiovascular deconditioning.
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Behavior of B-type natriuretic peptide during mechanical ventilation and spontaneous breathing after extubation.
Principi, T, Falzetti, G, Elisei, D, Donati, A, Pelaia, P
Minerva anestesiologica. 2009;(4):179-83
Abstract
BACKGROUND The behavior of B-type natriuretic peptide (BNP) is assessed during mechanical ventilation (MV) and spontaneous breathing after extubation in critical patients. METHODS Thirty patients admitted in the Intensive Care Unit (ICU) were enrolled. BNP, fluid balance (FB), airway pressure (AP) and dobutamine infusion needing (DP) were registered in three stages: T0, admission to ICU; T1, before extubation; T2, 24 h after extubation. RESULTS Patients with congestive heart failure (CHF) had BNP values higher than other patients. The value of BNP during MV was greater than normal in all patients. The cut-off to discriminate patients with heart failure during MV was 286 pgxmL(-1)(sensitivity: 86%; specificity: 90%). The increase of BNP during MV directly correlated with FB and inversely correlated with AP and DP. The plasmatic level of BNP remained higher than normal values 24 h after extubation. CONCLUSIONS The underlying disease of an ICU patient seems to play a relevant role for BNP production and is probably linked to different aspects of therapeutic approach required by the patient. Our data suggest a cut-off value of BNP higher than the usual is necessary to discriminate mechanically-ventilated patients without CHF. This study should be repeated with an enlarged population.
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Immunomodulation in type 1 diabetes by NBI-6024, an altered peptide ligand of the insulin B epitope.
Alleva, DG, Maki, RA, Putnam, AL, Robinson, JM, Kipnes, MS, Dandona, P, Marks, JB, Simmons, DL, Greenbaum, CJ, Jimenez, RG, et al
Scandinavian journal of immunology. 2006;(1):59-69
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Abstract
NBI-6024 is an altered peptide ligand (APL) corresponding to the 9-23 amino acid region of the insulin B chain (B(9-23)), an epitope recognized by inflammatory interferon-gamma-producing T helper (Th)1 lymphocytes in type 1 diabetic patients. Immunomodulatory effects of NBI-6024 administration in recent-onset diabetic patients in a phase I clinical trial (NBI-6024-0003) were measured in peripheral blood mononuclear cells using the enzyme-linked immunosorbent spot assay. Analysis of the mean magnitude of cytokine responses to B(9-23) and NBI-6024 for each cohort showed significant increases in interleukin-5 responses (a Th2 regulatory phenotype) in cohorts that received APL relative to those receiving placebo. A responder analysis showed that Th1 responses to B(9-23) and NBI-6024 were observed almost exclusively in the placebo-treated diabetic population but not in nondiabetic control subjects and that APL administration (five biweekly subcutaneous injections) significantly and dose-dependently reduced the percentage of patients with these Th1 responses. The results of this phase I clinical study strongly suggest that NBI-6024 treatment shifted the Th1 pathogenic responses in recent-onset type 1 diabetic patients to a protective Th2 regulatory phenotype. The significance of these findings on the clinical outcome of disease is currently under investigation in a phase II multidose study.
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Cholesterol, copper and Abeta in controls, MCI, AD and the AD cholesterol-lowering treatment trial (ADCLT).
Sparks, DL, Petanceska, S, Sabbagh, M, Connor, D, Soares, H, Adler, C, Lopez, J, Ziolkowski, C, Lochhead, J, Browne, P
Current Alzheimer research. 2005;(5):527-39
Abstract
Cholesterol clearly plays an influential role in promoting the production of amyloid beta (Abeta) and possibly the progression of Alzheimer's Disease (AD). The AD Cholesterol-Lowering Treatment trial (ADCLT; 1 year duration) tested atorvastatin and found significant benefit on measures of cognition and depressive symptoms in treated patients (N = 32) compared to placebo (N = 31). We assessed the circulating levels of Abeta(1-40), Abeta(1-42), ceruloplasmin (copper chaperone), apolipoprotein E and HDL-cholesterol in blood collected at each clinical visit during the ADCLT. We also determined the circulating cholesterol, ceruloplasmin, and Abeta levels in AD and MCI (mild cognitive impairment) patients, and controls (two groups stratified by function; high and low) participating in our Brain Bank Program. Each Brain Bank individual was clinically assessed for performance on the Mini-Mental Status Exam (MMSE), Rey auditory verbal learning test (AVLT), Clock draw, and UPSIT (smell identification test). Among individuals of equal age and education, scores on the MMSE were significantly reduced in AD compared to both MCI and controls, as were scores on the UPSIT. Ability on delayed verbal recall was significantly reduced in AD compared to MCI, and in MCI compared to both control groups. Performance on the Clock draw was similar for AD and MCI patients, but was significantly reduced when comparing MCI to control. Both cholesterol and ceruloplasmin levels were significantly increased in low-function controls compared to the high-function control group, but were not different from levels identified in the MCI and AD patients. Significantly increased levels of Abeta(1-40) occurred in low- compared to high-function controls, with a further significant increase in MCI compared to low-function controls. Circulating Abeta(1-40) levels were decreased in AD compared to MCI. Levels of Abeta(1-42) were not significantly different between the groups. The slight gradual increase in circulating Abeta(1-40) and Abeta(1-42) levels produced by atorvastatin treatment in the ADCLT were not significant compared placebo. There was a trend for significant reduction in circulating ceruloplasmin levels after a year of atorvastatin therapy compared to levels observed at screen. The levels of HDL-cholesterol remained stable in the atorvastatin treated AD patients for 9 months and then decreased significantly compared to the placebo group at the 1-year time-point. The combined data support a role for cholesterol in AD and a possible influence of increasing circulating copper levels. The deterioration of function in controls and transition to MCI may be associated with concomitant incremental increases in circulating Abeta(1-40) levels. Increased cholesterol and ceruloplasmin levels may be associated with slight deterioration in function among controls as a precursor to impairment considered MCI. The clinical benefit of atorvastatin therapy is clearly not associated with decreased circulating Abeta or increased HDL-cholesterol, but a positive influence of reduced copper (ceruloplasmin) levels may be a consideration.
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Sodium status and angiotensin-converting enzyme inhibition: effects on plasma angiotensin-(1-7) in healthy man.
Kocks, MJ, Lely, AT, Boomsma, F, de Jong, PE, Navis, G
Journal of hypertension. 2005;(3):597-602
Abstract
OBJECTIVE Angiotensin-converting enzyme (ACE) inhibitors provide effective intervention for cardiovascular and renal disease. Changes in angiotensin-(1-7) have been proposed to be involved in the mechanism of action of ACE inhibition (ACEi). In particular, an altered balance between angiotensin II and angiotensin-(1-7) might be involved. A shift in sodium status modifies the activity of the renin-angiotensin-aldosterone system and the effects of ACEi, but its effects on angiotensin-(1-7) are unknown. We therefore studied the effect of a shift in sodium intake on angiotensin-(1-7), during placebo and ACEi. METHODS A double-blind, placebo-controlled study was conducted in 17 healthy men. The subjects were studied for two 2-week periods: 20 mg/day enalapril and placebo. The first week of each period they used a 50 mmol Na+ diet [low sodium (LS)], the second week a 200 mmol Na+ diet. Angiotensin levels and blood pressure were measured at the end of each week. RESULTS During placebo, LS intake elicited a three-fold rise in ang-(1-7) that paralleled the rise in other components of the renin-angiotensin system. During ACEi LS did not affect angiotensin II, but did induce a clear-cut rise in angiotensin-(1-7)--to the extent that angiotensin-(1-7) was highest during combination of ACEi and LS. Consequently, during ACEi LS shifted the balance between angiotensin-(1-7) and angiotensin II towards angiotensin-(1-7). CONCLUSION The sodium status modifies levels of angiotensin-(1-7). During ACEi angiotensin-(1-7) is still subject to stimulation by sodium restriction, and provides opportunity for therapeutic manipulation. Exploration of this opportunity in patient populations may lead to strategies to improve therapeutic benefits of ACEi.
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Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion.
Nikolaidis, LA, Mankad, S, Sokos, GG, Miske, G, Shah, A, Elahi, D, Shannon, RP
Circulation. 2004;(8):962-5
Abstract
BACKGROUND Glucose-insulin-potassium infusions are beneficial in uncomplicated patients with acute myocardial infarction (AMI) but are of unproven efficacy in AMI with left ventricular (LV) dysfunction because of volume requirements associated with glucose infusion. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties that stimulate glucose uptake without the requirements for concomitant glucose infusion. METHODS AND RESULTS We investigated the safety and efficacy of a 72-hour infusion of GLP-1 (1.5 pmol/kg per minute) added to background therapy in 10 patients with AMI and LV ejection fraction (EF) <40% after successful primary angioplasty compared with 11 control patients. Echocardiograms were obtained after reperfusion and after the completion of the GLP-1 infusion. Baseline demographics and background therapy were similar, and both groups had severe LV dysfunction at baseline (LVEF=29+/-2%). GLP-1 significantly improved LVEF (from 29+/-2% to 39+/-2%, P<0.01), global wall motion score indexes (1.94+/-0.11-->1.63+/-0.09, P<0.01), and regional wall motion score indexes (2.53+/-0.08-->2.02+/-0.11, P<0.01) compared with control subjects. The benefits of GLP-1 were independent of AMI location or history of diabetes. GLP-1 was well tolerated, with only transient gastrointestinal effects. CONCLUSIONS When added to standard therapy, GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty.