Atrial Natriuretic Peptide Levels Research Articles

The role of Atrial Natriuretic Peptide in the development of renal and cardiac damage in a Dahl SS rat model

Atrial natriuretic peptide (ANP), encoded by the Nppa gene, is an osmoregulatory hormone that promotes salt excretion. A GWAS identified ANP as a causative factor of blood pressure development, and in humans ANP levels are suggested as an indicator of salt‐sensitivity. Recently, Flister et al. (Genome Res, 2013) generated a knockout of Nppa in the Dahl Salt‐Sensitive (SS) rat background (further referred to as the SSNPPA−/− rat). The aim of the current study was to provide mechanistic insights into the effects of ANP deficiency on renal and cardiac function in the Dahl SS rats.In this study hypertension was induced in SSNPPA−/− and control Dahl SS rats by placing them on a high salt diet (HS, 4% NaCl) for 21 days. A combination of in vivo techniques (blood pressure monitoring and GFR measurements) with ex vivo imaging, electrophysiological, and biochemical methods were used to test the role of ANP deficiency in the development of SS hypertension. Immunohistochemical analysis was employed to assess renal and cardiac damage.Chronic i.v. infusion of ANP in wild type SS rats (100 ng/kg/day) attenuated the salt‐induced increase in blood pressure in the wild type SS rats, whereas SSNPPA−/− rats demonstrated a significantly higher mean arterial pressure compared to SS controls when the rats were fed a HS diet: on day 21 of diet MAP was 185.8 ± 9 mmHg in SSNPPA−/− rats compared to 144.6 ± 4 mmHg in SS controls. Additionally, SSNPPA−/− rats showed exacerbated kidney damage as revealed by intensified kidney hypertrophy, higher glomerular injury scores, and increased renal arterial hypertrophy. GFR was found to be reduced in the control SS rats fed a HS diet compared to LS diet, however significance was not reached in the SSNPPA−/− group. SSNPPA−/− rats did exhibit reduced diuresis, as well as a trend for lower sodium and chloride excretion when fed a HS diet. The activity of Epithelial Sodium Channel (an important contributor to the development of SS hypertension) was found to be increased in the cortical collecting ducts of the SSNPPA−/− rats. Additionally, SSNPPA−/− rats fed a HS diet showed intensified cardiac damage compared to SS controls, as demonstrated by higher heart to body weight ratio, and a dramatically elevated interstitial fibrosis. However, ultrasound echocardiography revealed that although SSNPPA−/− rats have cardiac remodeling, they do not exhibit heart failure.Therefore, ANP is major regulator in the development of SS hypertension, and its deficiency leads to more severe cardiac and kidney damage. Further work will be devoted to discovering specific ANP‐associated molecular pathways that mediate its effects in SS hypertension, and assessing the therapeutic benefits of ANP for treating cardiovascular diseases.Support or Funding InformationMCW RAC Pilot Grant (DVI) and NIH HL10880 (AS)

Acute Supramaximal Exercise-Induced Adiponectin Increase in Healthy Volunteers: Involvement of Natriuretic Peptides

Exercise may modulate lipolysis via leading to natriuretic peptide secretion and beta-adrenergic activation. Adiponectin, an adipose-secreted multifunctional signaling protein, may be the missing link between exercise and lipolytic activity. In this study, we aimed to investigate the effects of supramaximal exercise on plasma levels of adiponectin, atrial natriuretic peptide (ANP), and B-type natriuretic peptide (BNP) in healthy humans. Thirty-one healthy young adult volunteers (male/female, 15/16; mean age±SD, 20.7±1.7 years) underwent a 30-second Wingate anaerobic exercise test on a cycle ergometer and venous blood sampling before and after the exercise test. Plasma ANP and BNP levels were assayed by radioimmunoassay, whereas adiponectin levels were assayed by enzyme-linked immunosorbent assay. Systolic and diastolic blood pressures, heart rate, hematocrit levels and blood lactate were also measured before and after exercise. The mean plasma adiponectin level significantly increased following a 30-second anaerobic exercise test compared to resting level (17.45±4.70 vs 31.29±5.16 μg/mL, respectively, p<0.001). The mean plasma ANP and BNP levels remained comparable before and after the 30-second anaerobic exercise. A 30-sec supramaximal exercise session enhanced circulating adiponectin levels in both gender groups, whereas ANP and BNP levels exerted non-significant alterations. We suggest that acute anaerobic exercise may affect secretory function of adipose tissue which seems not related with natriuretic peptide secretion.

The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen improve ANP levels and decrease nuclear translocation of NF-kB in estrogen-deficient rats.

The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported. We investigated the effects of raloxifene and tamoxifen on ANP signaling, p65 NF-kB nuclear translocation, cardiac histology and contractility. Female rats were divided into five groups: control (SHAM), ovariectomized (OVX), OVX-treated 17-β-estradiol (E), OVX-treated raloxifene (RLX) and OVX-treated tamoxifen (TAM). The treatments started 21days after ovariectomy and continued for 14days. Ovariectomy reduced ANP mRNA in the left atrium (LA), decreased the content of ANP protein in the LA and in plasma, and increased the level of p65 NF-kB nuclear translocation in the left ventricle. Both 17-β-estradiol and SERMs were able to reverse these alterations, which were induced by the estrogen deficient state. The hemodynamic and cardiac structural parameters analyzed in the present work were not modified by the interventions. Our study demonstrates, for the first time, the additional benefits of raloxifene and tamoxifen in an estrogen-deficient state. These include the normalization of plasmatic and cardiac ANP levels and cardiac p65 NF-kB translocation. Therefore, these treatments promote cardiovascular protection and may contribute to the prevention of cardiac dysfunction observed long-term in postmenopausal women.

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload‐induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.

Effects of ZFP580 on ventricular remodeling after myocardial ischemia/reperfusion in rats

To investigate the relationship between zinc finger protein(ZFP580)and ventricular remodeling after myocardial is-chemia/reperfusion(I/R) injury in rats. Seventy-two rats were divided into sham group and I/R groups which would be tested in se-ries time of 0.5 h, 1 h, 2 h, 4 h, 1 d,7 d,14 d,28 d after reperfusion to observe the expression of ZFP580 in rat myocardium. The H9C2 cells were cultured and treated with transforming growth factor-beta1 (TGF-β 1) to establish cardiac hypertrophy in vitro model in series time of 0 h, 8h, 16 h and 24 h. The cardiomyocyte hypertrophy morphology was measured. The mRNA levels of atrial natriuretic peptide(ANP), myosin heavey chain beta(β -MHC) and ZFP580 genes were quantified. The protein levels of MMP-3 and ZFP580 were quantified after H9C2 cells were transfected by lentiviral-mediated ZFP580 gene. Myocardial I/R injury model was successfully established. Myocardial tis-sue in rats had large area infarction, and myocardial cells were eosinophilic changed. The increased level of ZFP580 protein was observed in the cardiomyocytes around infarction zone. The expression of TGF-β 1 in myocardium was up-regulated after myocardial I/R injury. TGF-β 1 (5 ng/ml) treatment could induce cardiomyocyte hypertrophy in H9C2 cells. TGF-β 1 treatment increased the cell size and mRNA levels of ANP andβ -MHC genes (P < 0.05), which represent degree of cardiac hypertrophy. TGF-β 1 treatment also increased the protein levels of ZFP580 in H9C2 cells (P < 0.05). In the H9C2 cells transfected by lentiviral-mediated gene, the protein level of MMP3 was decreased (P < 0.05). ZFP580 is probably related with ventricular remodeling after myocardial I/R injury by involving TGF-β 1 induced cardiomyocyte hypertrophy and attenuating MMP-3 production.

Zinc Prevents the Development of Diabetic Cardiomyopathy in db/db Mice.

Diabetic cardiomyopathy (DCM) is highly prevalent in type 2 diabetes (T2DM) patients. Zinc is an important essential trace metal, whose deficiency is associated with various chronic ailments, including vascular diseases. We assessed T2DM B6.BKS(D)-Leprdb/J (db/db) mice fed for six months on a normal diet containing three zinc levels (deficient, adequate, and supplemented), to explore the role of zinc in DCM development and progression. Cardiac function, reflected by ejection fraction, was significantly decreased, along with increased left ventricle mass and heart weight to tibial length ratio, in db/db mice. As a molecular cardiac hypertrophy marker, atrial natriuretic peptide levels were also significantly increased. Cardiac dysfunction and hypertrophy were accompanied by significantly increased fibrotic (elevated collagen accumulation as well as transforming growth factor β and connective tissue growth factor levels) and inflammatory (enhanced expression of tumor necrosis factor alpha, interleukin-1β, caspase recruitment domain family member 9, and B-cell lymphoma/leukemia 10, and activated p38 mitogen-activated protein kinase) responses in the heart. All these diabetic effects were exacerbated by zinc deficiency, and not affected by zinc supplementation, respectively. Mechanistically, oxidative stress and damage, mirrored by the accumulation of 3-nitrotyrosine and 4-hydroxy-2-nonenal, was significantly increased along with significantly decreased expression of Nrf2 and its downstream antioxidants (NQO-1 and catalase). This was also exacerbated by zinc deficiency in the db/db mouse heart. These results suggested that zinc deficiency promotes the development and progression of DCM in T2DM db/db mice. The exacerbated effects by zinc deficiency on the heart of db/db mice may be related to further suppression of Nrf2 expression and function.

Evaluation of Long-Term Combination Therapy With Peritoneal Dialysis and Hemodialysis.

It is well known that a combination therapy with peritoneal dialysis (PD) and hemodialysis (HD) is feasible and may improve clinical status in patients for whom adequate solute and fluid removal is difficult to achieve with PD alone. The objective of the present study was to evaluate whether the therapy is useful in the likelihood of long-term peritoneal membrane and cardiac function. The therapy was 6days of PD and one session of HD per week. Physical, biochemical, dialysate-to-plasma ratio of creatinine (D/P Cr), arteriovenous fistula (AVF) blood flow, and left ventricular mass index (LVMI) data were prospectively analyzed in 30 patients with measurements performed at 0 and 6months, and for 21 patients, 12 or 18months after initiation of the therapy. The levels of hemoglobin (Hb) after therapy were significantly higher than those at the initiation of therapy. The levels of LVMI and human atrial natriuretic peptide (hANP) after therapy were significantly lower than those at the initiation of therapy, whereas AVF blood flow did not change significantly. D/P Cr levels at 6months after the therapy were significantly lower than those at the initiation of therapy. D/P Cr levels at 12 or 18months after the therapy were not aggravated. It appears that the therapy improves Hb levels and cardiac function because of adjusting body fluid status. It was indicated that peritoneal function after therapy may be improved. Therefore, combination therapy is useful from the lifestyle viewpoint of patients in the transition period of PD to HD with end-stage kidney disease.

Changes in Plasma Levels of Atrial Natriuretic Peptide and B-Type Natriuretic Peptide after Surgical Therapy of Atrial Fibrillation

Objective: In patients undergoing surgical therapy of atrial fibrillation (AF), left atrial appendage (LAA) amputation is discussed controversially, because the LAA is a hormone-producing organ. We examined patients after surgical AF therapy with or without LAA amputation to determine the influence of LAA amputation on ANP and BNP plasma levels.

Obstructive sleep-disordered breathing, enuresis and combined disorders in children: chance or related association?

Nocturnal enuresis is usually diagnosed and treated by a primary paediatrician or family practitioner; if there is any doubt, the children may be referred to a paediatric urologist. Obstructive sleep-disordered breathing is a complex, multifactorial disorder. Adenotonsillar hypertrophy is considered an important factor associated with obstructive sleep apnoea syndrome. Enuresis and obstructive sleep-disordered breathing are both frequent problems of sleep in childhood. We conducted an electronic search in Medline, Scopus and the ISI Web of Science to look for published material and identify a putative link between nocturnal enuresis and obstructive sleep-disordered breathing. A total number of 98 documents were found, but 24 of these had to be excluded after an attentive reading of the title, abstract or full text because the information therein was not suitable for the aims of our search. Studies have found that children with obstructive sleep apnoea syndrome frequently also have nocturnal enuresis. Both disorders have an underlying sleep disturbance characterised by an altered arousal response and sleep fragmentation. The pathophysiology of enuretic events is seemingly linked to nocturnal obstructive events, causing increased intra-abdominal pressure and altered systemic blood pressure that induces natriuresis and polyuria by altering levels of antidiuretic hormone, and atrial and brain natriuretic peptides. We found 17 studies regarding the urological outcome of treatment for obstructive sleep-disordered breathing in children with enuresis. Although a vast amount of information is now available regarding the relationship between nocturnal enuresis and obstructive sleep-disordered breathing, many of the published studies were uncontrolled, retrospective or prospective cohort studies (grade C recommendation). Resolution of enuresis after medical or surgical treatment for obstructive sleep-disordered breathing has been emphasised. Consequently, symptoms such as snoring, sleep apnoeas and restless sleep should be sought for all children with enuresis. Confirmed obstructive sleep-disordered breathing should be treated promptly; subsequently, the persistence of enuresis requires treatment following the standard protocol.

Comparison of Pulmonary Venous and Left Atrial Remodeling in Patients With Atrial Fibrillation With Hypertrophic Cardiomyopathy Versus With Hypertensive Heart Disease

Left ventricular diastolic dysfunction in hypertrophic cardiomyopathy (HC) increases susceptibility to atrial fibrillation. Although phenotypical characteristics of the hypertrophied left ventricle are clear, left atrial (LA) and pulmonary venous (PV) remodeling has rarely been investigated. This study aimed to identify differences in LA and PV remodeling between HC and hypertensive heart disease (HHD) using 3-dimensional computed tomography. Included were 33 consecutive patients with HC, 25 with HHD, and 29 without any co-morbidities who were referred for catheter ablation of atrial fibrillation. Pre-ablation plasma atrial and brain natriuretic peptide levels, post-ablation troponin T level, and LA pressure were measured, and LA and PV diameters were determined 3 dimensionally. LA transverse diameter in the control group was smaller than that in the HHD or HC group (55 ± 6 vs 63 ± 9 vs 65 ± 12mm, p= 0.0003). PV diameter in all 4 PVs was greatest in the HC group and second greatest in the HHD group (21.0 ± 3.1 vs 23.8 ± 2.8 vs 26.8 ± 4.1mm, p <0.0001 for left superior PV). Differences in PV size between the HHD and HC groups were enhanced by indexing to the body surface area (12.4 ± 1.9 vs 13.1 ± 1.4 vs 16.1 ± 3.3mm/m2, p <0.0001). The PV/LA diameter ratio was greater in the HC than in the other groups (0.38 ± 0.06 vs 0.38 ± 0.05 vs 0.42 ± 0.07, p= 0.01). Atrial natriuretic peptide, brain natriuretic peptide, troponin T levels, and LA pressure were highest in the HC group (all p <0.05). In conclusion, the stiff LA caused from atrial hypertrophy may account for higher levels of biomarkers, higher LA pressure, and PV-dominant remodeling in HC.

Comparison of Plasma Levels of Renin, Vasopressin and Atrial Natriuretic Peptide in Hypertensive Amlodipine Induced Pedal Oedema, Non-Oedema and Cilnidipine Treated Patients.

Amlodipine is a third generation dihydropyridine group of calcium channel blocker and having an excellent antihypertensive profile. Pedal Oedema (PE) is the major drawback of amlodipine therapy and the incidence of Amlodipine Induced Pedal Oedema (AIPE) has been found significantly high. Several neurohumoral factors influence the incidence of oedema. We aimed to compare the plasma levels of renin, vasopressin and atrial natriuretic peptide in hypertensive AIPE, non-oedema and cilnidipine treated patients. The present prospective, interventional study was conducted on 104 mild to moderate hypertensive patients (52 patients in each group), after due consideration of eligibility criteria. Plasma Renin (PR), Vasopressin (VAS), and the Atrial Natriuretic Peptide (ANP) was estimated by ELISA test and compared between the AIPE, Amlodipine Treated Non-Oedema (ATNE) in Phase I, and AIPE and Cilnidipine Treated (CT) Groups in Phase II. The clinical and demographic parameters were matched. PR was significantly high in AIPE group than the ATNE, and it was significantly reduced after one month follow up with the substitution of cilnidipine. The median (IQR) value of PR was 4.87 (3.58, 6.63), 3.50 (1.44, 5.47) and 2.66 (1.02, 5.66) ng/ml in AIPE, ATNE, CT group respectively. VAS was significantly high in AIPE group than ATNE, and it significantly reduced after one month follow up with CT group. The median (IQR) value of vasopressin was 6.78 (2.55, 9.16), 2.58 (1.61, 5.73) and 2.50 (1.23, 5.00) ng/ml in AIPE, ATNE and CT groups respectively. There was no significant difference seen in plasma ANP levels between the groups. The p-value was <0.05 which is statistically significant. The AIPE may not be volume overload or fluid retention; it may be due to persistent raise in adrenergic activity followed chronic amlodipine therapy. Cilnidipine relatively suppresses the sympathetic activity, and completely resolves the AIPE by significantly reducing PR and VAS levels. ANP did not show a difference between groups. Cilnidipine is the suitable alternative antihypertensive drug for AIPE patients.

PLASMA CONCENTRATIONS AND CORRELATIONS OF NATRIURETIC PEPTIDES AND OXYTOCIN DURING LABOR AND EARLY POSTPARTUM PERIOD.

Natriuretic peptides (NP) and oxytocin (OT) play an important role in cardiovascular and hydro-electrolytic homeostasis. Changes in NP levels and their roles in cardiovascular adaptations in pregnancy and labor have not been clear. The present study aimed to investigate the changes and correlations in plasma levels of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), B-type natriuretic peptide (BNP) and OT during labor and the postpartum period. Blood samples were collected from 29 healthy pregnant women in the active phase of spontaneous labor, 15 minutes after delivery and 3 hours postpartum. Plasma levels of OT and the stable N-terminal fragments of NPs (NT-proANP, NT-proCNP, NT-proBNP) were measured using enzyme or electrochemiluminescence immunoassays. The plasma levels of NT-proANP and NT-proCNP significantly decrease 3 hours postpartum compared to the active phase of labor and to 15 minutes after delivery. The plasma NT-proBNP levels significantly higher after delivery and 3 hours postpartum compared to the active phase of labor. A significant correlation exists between OT and NT-proANP levels during the active phase of labor and 15 minutes after delivery. The data show that during labor and postpartum, the plasma concentrations of the NPs change differently. Elevations in NT- proBNP after delivery suggest that BNP may be involved in postpartum adaptations. The correlations between OT and ANP levels indicate that OT may be partly responsible for the increased levels of ANP and may have a role in the modification of the cardiovascular system.

Serum atrial natriuretic peptide: a suspected biomarker of breast cancer.

Aim of the studyTo assess serum levels of ANP in breast cancer female patients and its relationship to metastasis and some clinical parameters among those patients.Material and methodsOne hundred breast cancer patients with and without metastasis along with 20 healthy closely matched controls, were enrolled in the present cross sectional study. Background: To assess the serum levels of atrial natriuretic peptide in breast cancer Serum levels of ANP were assessed using ELISA.ResultsMean serum levels of ANP breast cancer patients (13.9 ±10.1 ng/ml) were significantly elevated compared to healthy control group (2.2 ±1.3 ng/ml) (p < 0.001). The metastatic breast cancer patients showed significant elevated ANP levels (17.1 ±8.9 ng/ml) compared to non-metastatic group (6.4 ±8.8 ng/ml) p < 0.001. Within the metastatic group significant difference was detected between de novo metastatic, under follow-up, under hormonal control and locally advanced group (p = 0.007).ConclusionsThis study showed significant elevated levels of ANP in the serum of metastatic breast cancer patients compared to non-metastatic patients. Within the metastatic group the lowest levels were detected in metastatic breast Cancer under hormonal treatment either tamoxifen or aromatase inhibitor.

Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Facilitates the Development of Cardiac Hypertrophy

Background/Aims: Adult cardiomyocytes can re-enter cell cycle as stimulated by prohypertrophic factors although they withdraw from cell cycle soon after birth. p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution to this process remains largely unclear. Methods: The gene expression profile in left ventricle (LV) of spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats was determined using quantitative PCR array and verified by real-time PCR and Western blotting. Hypertrophic response of H9c2 cells and neonatal rat ventricular myocytes (NRVM) were induced by angiotensin II (1 µmol/L). Cardiac hypertrophy of mice was elicited by isoproterenol (ISO) infusion (40 mg/kg per day for 14 days). p21-adenovirus and p21-siRNA were employed to transfect NRVM, and sterigmatocystin (STE, 3 mg/kg, ip, qd) was used to inhibit p21 activity. mRNA and protein expression levels of α- and β-myosin heavy chain (MHC), p21WAF1/CIP1, calcineurin (CaN) and atrial natriuretic peptide (ANP) were assayed by realtime PCR and WB, respectively. Results: Sixteen genes showed two-fold or greater changes between SHR and WKY rats, in which the expression of p21WAF1/CIP1 was upregulated by 4.15-fold (P=0.002) and reversed by losartan. Surface area, protein content, mRNA and protein expressions of β-MHC, ANP and p21WAF1/CIP1 in H9c2 cells treated with AngII elevated significantly compared with control group. p21-Ad transfection markedly increased the surface area and β-MHC mRNA expression of normal NRVMs, and p21-siRNA transfection decreased them in AngII-treated NRVMs. STE treatment decreased HW/BW and cross-sectional area, expression levels of β-MHC, ANP and p21 significantly in ISO-treated mice. Conclusion: Our findings suggest that p21 facilitates the development of cardiac hypertrophy, and regulating the expression of p21 may be an approach to attenuate hypertrophic growth of cardiomyocytes.

心臓手術患者における睡眠呼吸障害: NU-SLEEP trial

Abstract Background Sleep disordered breathing (SDB) is associated with lifestyle-related diseases and its treatment influence the prognosis of cardiac disease, but little investigation of SDB has been conducted in cardiac surgery patients. Methods and results A prospective study was performed in 1005 patients undergoing cardiac surgery. The primary endpoint was the severity of SDB determined from the apnea/hypopnea index. The secondary endpoints were patient background factors, cardiovascular risk factors, ejection fraction, atrial and brain natriuretic peptides, oxidative stress and inflammatory markers, and postoperative atrial fibrillation. While 227 patients (22.6%) did not have SDB, there were 361 patients (35.9%) with mild SDB, 260 patients (25.9%) with moderate SDB, and 157 patients (15.6%) with severe SDB. Patients with severe SDB had a lower ejection fraction and higher levels of atrial and brain natriuretic peptides than the other groups. Postoperative atrial fibrillation occurred in 28 patients without SDB (13.6%), 43 patients with mild SDB (13.5%), 74 patients with moderate SDB (31.9%), and 73 patients with severe SDB (52.5%), being significantly more frequent in the severe group than the other groups. Conclusions SDB was frequent in cardiac surgery patients. Activation of the renin–angiotensin–aldosterone system, postoperative atrial fibrillation atrial, and cardiac dysfunction were associated with severe SDB. Markers of inflammation and oxidative stress also increased as SDB became more severe.

High levels of atrial natriuretic peptide and copeptin and mortality risk

Abstract Objective To determine whether high levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin (PCT) plasma concentrations are associated with increased mortality risk. Methods Prospective observational study including 254 critically ill children. MR-proANP, copeptin and PCT were compared between children with high (Group A; n = 33) and low (Group B; n = 221) mortality risk, and between patients with failure of more than 1 organ (Group 1; n = 71) and less than 2 (Group 2; n = 183). Results Median (range) of MR-proANP, copeptin, and PCT levels in group A vs B were, respectively: 209.4 (30.5–1415.8) vs. 75.0 (14.6–867.2) pmol/L (P Conclusions High levels of MR-proANP, copeptin and PCT were associated with increased mortality risk scores. MR-proANP showed a higher association than copeptin with number of organs in failure.

Impact of Atrial Natriuretic Peptide Value for Predicting Paroxysmal Atrial Fibrillation in Ischemic Stroke Patients

The impact of atrial natriuretic peptide (ANP) value for predicting paroxysmal atrial fibrillation (pAF) in ischemic stroke patients remains uncertain. The consecutive 222 ischemic stroke patients (median 77 [IQR 68-83] years old, 93 females) within 48 hours after onset were retrospectively studied. Plasma ANP and brain natriuretic peptide (BNP) levels were simultaneously measured at admission. Of all, 158 patients had no evidence of atrial fibrillation (AF) (sinus rhythm [SR] group), 25 patients had pAF (pAF group), and the other 39 patients had chronic AF (cAF group). We investigated predicting factors for pAF, with focus on ANP, BNP, and ANP/BNP ratio. ANP value was significantly higher in the pAF than in the SR group (97 [50-157] mg/dL versus 42 [26-72] mg/dL, P < .05) and further increased in the cAF group (228 [120-392], P < .05 versus pAF and SR groups). Similarly, the BNP value was higher in the pAF than in the SR group (116 [70-238] mg/dL versus 34 [14-72] mg/dL, P < .05) and further increased in the cAF group (269 [199-423], P < .05 versus pAF and SR groups). ANP/BNP ratio was lower in the pAF and cAF groups than in the SR group (.6 [.5-1.2] and .7 [.5-1.0] versus 1.3 [.8-2.4], both P < .05]. Multivariate analysis in the SR and pAF groups (n = 183) demonstrated that age, congestive heart failure, ANP, and BNP, but not ANP/BNP ratio, were independent predictors for detecting pAF. Receiver operating characteristic curve analysis further showed that area under the curve was similar between ANP and BNP (.76 and .80). ANPmay be clinically useful for detecting pAF in ischemic stroke patients as well as BNP.

Abstract 13881: Determining Factors and Prognostic Value of Plasma γ- Atrial Natriuretic Peptide Ratio in Patients With Heart Failure

Background: Atrial natriuretic peptide (ANP) is a peptide hormone that maintain sodium homeostasis and inhibit activation of the renin-angiotensin-aldosterone system. Three endogenous molecular forms of human ANP, including fully bioactive α-ANP, β-ANP; an antiparallel dimer of α-ANP, and γ-ANP; α-ANP precursor, are present in heart and plasma of patients with heart failure (HF). However, the clinical importance of molecular ratio of ANP has not been evaluated. This study was designed to evaluate plasma γ-ANP and total amount of ANP levels (total ANP) in patients HF, and identify the determining factor and prognostic value of %γ-ANP (γ-ANP /total ANP ratio). Method and Results: We prospectively evaluated plasma γ-ANP and total ANP levels in 148 patients with acute decompensated HF before discharge using by chemiluminescence enzyme immunoassay. Median plasma total ANP and γ-ANP levels were 142.5 [63.2-231.3] and 10.9 [4.4-25.6] pmol/ml, respectively. %γ-ANP was 8.9 [5.5-15.2]% and significantly correlated with age (ρ=0.205; p=0.01), body mass index (BMI) (ρ=-0.316; p&lt;0.001), left ventricular ejection fraction (LVEF) (ρ=-0.250; p=0.002), hemoglobin (ρ=-0.182; p=0.03), and B-type natriuretic peptide (BNP) levels (ρ=0.393; p&lt;0.002). Patients with high %γ-ANP (≥ median value) were more likely to have ischemic etiology and prior HF hospitalization history. High %γ-ANP tended to increase all cause death (p=0.06) and was significantly associated with repeat HF-related hospitalization (p=0.01; Figure ). Conclusion: Increase of %γ-ANP was associated with older age, lower BMI, LVEF hemoglobin, and higher BNP levels. High %γ-ANP was a predictor of future HF-related rehospitalization. These results suggested that %γ-ANP was affected by presence of known poor prognostic factors of HF.

Plasma levels of atrial and brain natriuretic peptides in apparently healthy subjects: Effects of sex, age, and hemoglobin concentration

BackgroundTo examine whether the use of one value of natriuretic peptides to define “normal” is appropriate in all individuals, and to assess the influence of sex, age, and other variables on atrial and brain natriuretic peptides (ANP, BNP) levels. Methods and resultsA total of 1375 apparently healthy people (women:155, men:1220), aged 18–70years were enrolled. Both ANP and BNP levels were higher in women than in men (ANP: 12.50±6.82pg/mL vs 8.18±4.19pg/mL; BNP: 9.85±7.63pg/mL vs 7.03±6.97pg/mL). The subjects were divided into three age groups: group I, 18–30years; group II, 30–50years; group III, 50–70years. First, the influence of age on ANP and BNP levels was examined. In women, both ANP and BNP levels were higher in groups II and III than those in group I. In men, ANP and BNP levels increased with age. Second, sex differences in ANP and BNP levels due to age were examined. ANP level was higher in women than that in men in all age groups. BNP level was higher in women than that in men in groups I and II. Multivariate analysis indicated that both ANP and BNP levels were influenced by age, hemoglobin level, and platelet counts. ConclusionBecause ANP and BNP levels in healthy subjects are influenced by sex, age, and hemoglobin levels, the use of a single value to define “normal” in all individuals is not appropriate.

Sleep disordered breathing in cardiac surgery patients: The NU-SLEEP trial

BackgroundSleep disordered breathing (SDB) is associated with lifestyle-related diseases and its treatment influence the prognosis of cardiac disease, but little investigation of SDB has been conducted in cardiac surgery patients. Methods and resultsA prospective study was performed in 1005 patients undergoing cardiac surgery. The primary endpoint was the severity of SDB determined from the apnea/hypopnea index. The secondary endpoints were patient background factors, cardiovascular risk factors, ejection fraction, atrial and brain natriuretic peptides, oxidative stress and inflammatory markers, and postoperative atrial fibrillation. While 227 patients (22.6%) did not have SDB, there were 361 patients (35.9%) with mild SDB, 260 patients (25.9%) with moderate SDB, and 157 patients (15.6%) with severe SDB. Patients with severe SDB had a lower ejection fraction and higher levels of atrial and brain natriuretic peptides than the other groups. Postoperative atrial fibrillation occurred in 28 patients without SDB (13.6%), 43 patients with mild SDB (13.5%), 74 patients with moderate SDB (31.9%), and 73 patients with severe SDB (52.5%), being significantly more frequent in the severe group than the other groups. ConclusionsSDB was frequent in cardiac surgery patients. Activation of the renin–angiotensin–aldosterone system, postoperative atrial fibrillation atrial, and cardiac dysfunction were associated with severe SDB. Markers of inflammation and oxidative stress also increased as SDB became more severe.