Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5 +/- SEM 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 +/- 2.4 pg/ml) to day 7 (15.1 +/- 2.6 pg/ml). The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium 'escape' occurred by days 4 to 7. These results support the concept that ANP could play an important hormonal role in over-coming the sodium-retaining effects of mineralocorticoids in man.     

Decreased density of binding sites for atrial natriuretic peptide on platelets of patients with severe congestive heart failure

1. Binding sites for atrial natriuretic peptide (ANP) with a specificity similar to that of vascular ANP receptors have been demonstrated previously in human platelets. The density of these binding sites for ANP on platelets is decreased after increased dietary sodium intake, when plasma ANP levels increase. ANP-binding sites were investigated in patients with severe congestive heart failure (CHF), a condition in which there is an increase in the concentration of ANP in plasma. 2. In 24 patients with a clinical diagnosis of functional class III-IV CHF, plasma ANP (90.3 +/- 13.4 fmol/ml, mean +/- SEM) was significantly higher (P less than 0.001) than in 16 age-matched patients without cardiac disease (15.4 +/- 2.0 fmol/ml). The density of ANP-binding sites on platelets was significantly lower (P less than 0.01) in the 24 CHF patients (6.3 +/- 0.8 fmol/10(9) cells) than in the non-cardiac patients (11.8 +/- 1.4 fmol/10(9) cells). There was no significant difference in affinity of the ANP-binding sites between both groups. There was a significant non-linear inverse correlation of the density of ANP-binding sites on platelets with plasma ANP concentration. These results could not be explained by prior receptor occupancy secondary to the elevated concentration of circulating ANP. 3. In conclusion, ANP-binding sites on platelets are decreased in patients with severe CHF and with significantly elevated concentration of ANP in plasma.     

Prolonged decrease in blood pressure after atrial natriuretic peptide infusion in essential hypertension: a new anti-pressor mechanism?

1. To study the anti-hypertensive effects of atrial natriuretic peptide (ANP), eight patients with mild to moderate essential hypertension, on no treatment, were infused with alpha-human ANP (102-126) (37 pmol min-1 kg-1) or placebo for 60 min and observed for a further 4 h on the fifth day of low and high sodium diets in a randomized, cross-over study. 2. Plasma ANP levels increased over 30-fold into the high pathophysiological range during ANP infusion, but had returned to control values by 60 min after the end of infusion. With ANP infusion, there was a large decrease in supine blood pressure which was similar on both the low and high sodium intakes and was maximal 20-40 min after completion of the infusion. These reductions in blood pressure were sustained for a further 4 h after the end of ANP infusion and for 3 h after plasma ANP levels had returned to control values. 3. Maximal urinary sodium excretion increased 10-fold on the low sodium diet (negative sodium balance 20 mmol) and threefold on the high sodium diet (negative sodium balance 30 mmol) during ANP infusion; however, during the 4 h after infusion, urinary sodium excretion was below placebo values. During ANP infusion, packed cell volume increased significantly on both diets but returned to control values by 4 h after the end of infusion. 4. There were no significant changes in plasma renin activity compared with placebo during or after ANP infusion. However, plasma aldosterone was significantly greater than placebo values after the end of ANP infusion on both low and high sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide in human essential hypertension

We measured the circulating levels of atrial natriuretic peptide (ANP) in 62 patients with untreated uncomplicated essential hypertension and in 30 normotensive subjects. In the hypertensive patients, mean systolic and diastolic blood pressures were 148 and 101 mm Hg, respectively, and the mean heart rate was 73 beats/min. ANP concentrations were not elevated in the hypertensive group but were actually decreased slightly over those of the control group (27.4 +/- 1.8 pg/ml versus 35.3 +/- 2.4 pg/ml [P less than 0.02]). No relationship was found between ANP levels and diastolic blood pressure, plasma renin activity, urinary sodium excretion, or serum creatinine level. In 8 of the 62 patients with essential hypertension, 6 weeks of treatment with a dihydropyridine calcium channel blocker, nitrendipine, significantly reduced plasma ANP levels from 28.6 +/- 4.3 pg/ml to 18.7 +/- 1.8 pg/ml (P less than 0.05). In 17 additional patients treated with the hypotensive agent ketanserin, ANP levels were not significantly reduced after treatment. Thus, this study demonstrates that circulating plasma ANP levels are not increased but are slightly decreased in patients with uncomplicated essential hypertension in comparison with normotensive subjects. Furthermore, antihypertensive treatment with a calcium channel antagonist reduced plasma levels of ANP.     

Plasma atrial natriuretic peptide concentrations during exercise in sodium replete and deplete normal man

To explore the effects of exercise on plasma atrial natriuretic peptide (ANP) concentrations, eight normotensive volunteers performed maximal treadmill exercise in sodium replete and deplete states. Baseline immunoreactive plasma ANP concentrations were significantly lower during sodium depletion. During exercise plasma ANP rose in all subjects on both occasions. Plasma peptide responses were attenuated by sodium depletion with peak exercise levels only double baseline values, in contrast to the threefold increase in ANP concentrations observed when subjects were sodium replete. Plasma renin and aldosterone concentrations also rose with exercise. In contrast to changes in plasma ANP, the responses of both were enhanced by sodium depletion.     

Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake.     

Plasma concentrations of atrial natriuretic peptide in various diseases

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.     

Cardiac secretion and renal clearance of atrial natriuretic peptide in normal man: effect of salt restriction

1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet. 2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet. 3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (SED)+/- 14, P less than 0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (SED +/- 0.33, P less than 0.05). Brachial mean arterial pressure fell by 6% (P less than 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P less than 0.01), whereas arterial ANP concentrations fell by 39% (P less than 0.05). 4. Coronary sinus ANP levels fell from 417 to 268 pg/ml (SED +/- 74, P less than 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P less than 0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium restriction is due to reduced cardiac secretion.     

Paradoxical inhibition of atrial natriuretic peptide release during pacing-induced hypotension

1. To determine the influence of loss of atrioventricular synchrony on release of atrial natriuretic peptide (ANP), plasma ANP concentrations were measured by radioreceptor assay in 16 patients during sequential and ventricular cardiac pacing at normal heart rates. 2. Ventricular pacing induced an increase in plasma ANP concentrations (means +/- SEM) from 44 +/- 3 to 104 +/- 4 pmol/l (P less than 0.01) in 11 patients in whom systemic blood pressure was maintained. 3. In contrast, when ventricular pacing was associated with a fall in blood pressure (five patients), ANP levels (means +/- SEM) fell from 68 +/- 6 to 14 +/- 4 pmol/l (n = 5, P less than 0.05) within 5 min, despite an increase in atrial pressure. Plasma catecholamines also rose significantly in these latter patients. 4. We conclude that when loss of atrioventricular synchrony is well tolerated haemodynamically, cardiac release of ANP is increased in keeping with elevation in atrial pressure. However, the fall in plasma ANP concentration observed when ventricular pacing produces a fall in blood pressure suggests that in addition to atrial pressure, ANP release may be influenced by negative feedback mechanisms, possibly involving the baroreflex and autonomic nervous system.     

Influence of gender on circulating cardiac natriuretic hormones in patients with heart failure.

In order to study the influence of gender on circulating levels of cardiac natriuretic hormones (CNHs) in heart failure, we measured the plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by means of highly sensitive and specific IRMA methods in 239 consecutive patients (age 64.7 +/- 11.6 years, range 21-89 years; 170 men and 69 women) with cardiomyopathy. There was different response of CNH according to gender in patients with heart failure, as indicated by the ratio between the individual CNH values of patients and the gender-specific cut-off values. Indeed, the mean ratio for ANP found in men (3.6 +/- 3.6) was significantly higher (p = 0.0075) than that found in women (2.4 +/- 2.1). The mean ratio for BNP was on average 2.3 fold higher (15.9 +/- 27.1 in men and 6.9 +/- 6.8 in women, p = 0.0084). Moreover, age, ejection fraction, and disease severity independently and significantly contributed to regression with both ANP (R = 0.612, F = 39.969, p < 0.0001) and BNP (R = 0.656, F = 49.957, p < 0.0001) values, while gender did not. In conclusion, our study suggests a different, gender-specific activation of the CNH system in this clinical condition, although age, ejection fraction and disease severity seem to be more powerful predictors than gender of circulating levels of ANP and BNP in patients with heart failure.     

Plasma atrial natriuretic peptide: its relationship to changes in sodium intake, plasma renin activity and aldosterone in man

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP), plasma renin activity, aldosterone and vasopressin were measured in 11 normotensive subjects on a low (10 mmol/day), a normal (150 mmol/day) and a high (350 mmol/day) sodium intake. Plasma levels of IrANP increased significantly with increasing dietary sodium intake with levels (means +/- SD) of 3.9 +/- 2.1 pg/ml on the fifth day of the low sodium diet, 6.1 +/- 3.4 pg/ml on the fifth day of the normal sodium diet and 11.4 +/- 4.6 pg/ml on the fifth day of the high sodium diet. Plasma renin activity and aldosterone decreased significantly with increasing sodium intake whereas plasma vasopressin was highest on the high sodium intake. These results suggest that the atrial peptides may be a new and important component in the overall control of sodium and water balance during increased sodium intake.     

Diurnal variation of plasma atrial natriuretic peptide in normals and patients with enuresis nocturna.

The circadian variation of plasma atrial natriuretic peptide (ANP) in relation to urinary excretion of sodium (UNa) and potassium (UK) as well as clearance of creatinine (Ccrea) was assessed in 15 juvenile patients with enuresis nocturna and compared with 11 age-, sex-, and weight-matched normal subjects. Normal juveniles showed a highly significant diurnal variation (p less than 0.001) of plasma ANP with diurnal peak levels at midnight (0000 hours) and minimum levels at 0400 hours. Enuretic patients showed a similar diurnal rhythmicity with normal levels during day and night. In normals both UNa and UK showed significant diurnal rhythmicity with a marked reduction from daytime to night-time. Although the total diurnal excretions of UNa and UK were similar to normals, patients with enuresis showed abnormal diurnal variation in both UNa (p less than 0.05) and UK (p less than 0.01). The abnormal circadian rhythm of UNa and UK in enuretics seemed to be caused by abnormal tubular handling as similar abnormalities were found in the fractional excretions and as the circadian variation of Ccrea was normal. Especially during the first hours of sleep (2200 hours to 0000 hours), the patients showed polyuria (230 +/- 138 ml vs 116 +/- 58 ml, p less than 0.01), natriuresis (20.9 +/- 16.3 mmol l-1 vs 10.7 +/- 6.8 mmol l-1, p less than 0.01), and kaliuresis (7.3 +/- 6.3 mmol l-1 vs 3.7 +/- 2.3 mmol l-1, p less than 0.05), despite normal levels of plasma ANP. In conclusion, the study describes the diurnal variation of plasma ANP in relation to urinary excretion of sodium and potassium in a juvenile normal population. Patients with nocturnal enuresis show abnormal diurnal rhythmicity in the urinary excretion of sodium and potassium that is not correlated to the plasma levels of ANP.     

A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction.

Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50 +/- 11 vs. 158 +/- 37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4 +/- 2.4 vs. 0.6 +/- 0.4 ng/ml per h, P < 0.05) and aldosterone (36.4 +/- 12.5 vs. 2.5 +/- 0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion and regulation of the RAAS in experimental ELVD.     

窒息新生儿低钠血症与心钠素、抗利尿激素水平关系的研究

目的 :探讨血浆心钠素 (ANP)与抗利尿激素 (ADH)在窒息新生儿合并低钠血症中所起的作用及其临床意义。方法 :应用放射免疫分析法对 4 0例窒息新生儿血浆ANP、ADH水平变化进行动态观察 ,并与 2 0例正常足月儿进行对照 ,同时观察补液量对血清钠变化的影响。结果 :①新生儿窒息急性期血浆ANP、ADH水平明显增高 ,窒息程度越重 ,血浆ANP、ADH水平越高 ,血清钠水平越低 (P <0 0 1)。②限水组生后一周血清钠水平已恢复正常 ,未限水组血清钠明显低于正常。结论 :ANP、ADH可影响窒息新生儿水盐代谢 ,引起以稀释性低钠血症为主的稀释性和失钠性低钠血症。治疗应严格控制液体量 <3 0～ 50ml·kg- 1/d ,适当补钠 ,必要时可用速尿利尿     

Atrial natriuretic peptide and total exchangeable body sodium: relationships in rats with chronic myocardial infarction

1. The relationship between plasma atrial natriuretic peptide (ANP) and body sodium was determined in rats 1 month after myocardial infarction induced by coronary artery ligation. After operation rats received a normal or a low salt diet, and total exchangeable body sodium was measured sequentially. 2. Rats with infarction receiving a normal salt intake did not retain sodium when compared with sham-operated controls. Rats receiving a low salt diet had a 10% decrease in body sodium (P less than 0.01). The decrease was the same in rats with infarction as in controls. 3. Plasma ANP was similar in control rats irrespective of salt status. Plasma ANP levels were markedly elevated in rats with infarction irrespective of salt status (P less than 0.01). 4. The rise in plasma ANP was correlated with cardiac hypertrophy and infarct size in animals fed both normal and low salt diets. However, there was no relationship between plasma ANP and exchangeable body sodium. 5. These results suggest that in this model of heart failure plasma ANP is raised by increased left atrial stretch in proportion to the severity of left ventricular dysfunction. In contrast, plasma ANP concentrations do not appear to be elevated as a consequence of increased right atrial pressure caused by sodium retention and expanded extracellular volume.     

Effects of captopril and NaCl loading on plasma atrial natriuretic peptide (ANP) in rat with chronic heart failure

In order to study long term changes in plasma atrial natriuretic peptide (ANP) in chronic heart failure, plasma ANP levels were determined in rats after myocardial infarction due to coronary artery ligation and in sham-operated controls. In addition, effects of oral captopril treatment and sodium loading on plasma ANP were studied. In accordance with earlier reports plasma ANP paralleled both infarct size and signs of cardiac dysfunction. The highest plasma ANP levels were found in rats having over 45% of their left ventricle infarcted while rats with mild-to-moderate-size infarcts had only slightly elevated plasma ANP levels as compared with controls. These differences in plasma ANP levels between experimental and control groups remained remarkably stable during the three-month observation period. Plasma renin activity (PRA) was elevated in infarcted rats but no differences could be found between rats with varying infarct sizes. Captopril treatment decreased the high plasma ANP levels in rats with the largest infarcts, probably by unloading the failing heart. During increased sodium intake, plasma ANP levels increased in sham-operated controls but not in rats with heart failure. Thus, sodium loading, as compared with cardiac insufficiency, appears to be a weak stimulus for ANP release in rats. I conclude that plasma ANP is a sensitive marker, better than PRA, in long term follow-up of cardiac dysfunction.     

A sensitive radioimmunoassay of atrial natriuretic peptide in human plasma, using a tracer with an immobilized glycouril agent

A highly specific and sensitive radioimmunoassay (RIA) for alpha-human atrial natriuretic peptide (hANP[1-28]) in plasma was developed. The assay used a [125I]monoiodotyrosyl-hANP[1-28] tracer, prepared with an immobilized glycouril agent (Protag) and purified by high pressure liquid chromatography (HPLC), and a highly specific antiserum raised against hANP[1-28], coupled to keyhole limpet haemocyanin, in sheep. Plasma was extracted using C-18 Seppak cartridges. A good parallelism was found after dilution prior to extraction of plasma of patients with congestive heart failure (CHF) or of plasma of healthy subjects. Recovery of hANP[1-28] added to plasma was 96%. The limit of detection was 0.8 pg/tube, intra- and inter-assay variation were 9 and 12%, respectively. Mean plasma ANP values in 25 normal persons with a normal salt intake was 26.0 +/- 15.5 (+/- SD) pg/ml. Plasma levels of 18 subjects (7 normals, 11 CHF) were measured using four different antisera after the extraction step. High correlations were found between the values obtained with these four antisera.     

The relationship between atrial granularity and circulating atrial natriuretic peptide in hamsters with congestive heart failure

The BIO 14.6 strain of hamster is a model of familial cardiomyopathy complicated by congestive heart failure, sodium retention, and edema. In previous studies, bioassay techniques have demonstrated that the cardiac content of atrial natriuretic peptide (ANP) is reduced in these animals. On the basis of this observation, the syndrome of congestive heart failure has been hypothesized to be due to a deficiency in ANP. The current study was designed to correlate the cardiac content of ANP (determined by immunohistochemical techniques) with plasma circulating ANP (determined by radioimmunoassay). alpha-ANP antibodies were used for both determinations. The content of ANP in the atria was based on the degree of immunoreactive staining present (1 = lowest; 5 = highest), as graded by two observers. The mean granularity score of the cardiomyopathic hamsters was decreased (2.1 +/- 0.3) in comparison with that of age- and sex-matched control animals (3.5 +/- 0.5; P less than 0.05). In contrast, circulating immunoreactive ANP was higher in the hamsters with congestive heart failure than in the control animals--185.5 +/- 27.2 pg/ml versus 77.7 +/- 10.8 pg/ml (P less than 0.005). This study demonstrates that an inverse relationship exists between ANP content in the atria and circulating ANP. Furthermore, this study suggests that these hamsters with congestive heart failure are not deficient in ANP; rather, secretion of ANP is stimulated and storage of the peptide, represented by atrial granularity, is reduced.     

利钾尿肽与心钠素摩尔比在心房纤颤时的作用

目的 :探讨利钾尿肽 (KP)及 KP与心钠素 (ANP)摩尔比在心房纤颤 (房颤 )时的意义。方法 :用放射免疫 (放免 )分析法测定 2 3例阵发房颤患者和 2 4例持续房颤患者血浆中 KP与 ANP的水平 ,并以正常人作为对照。结果 :房颤患者血浆中 KP与 ANP的水平明显高于对照组 (P均 <0 .0 1) ,阵发房颤患者血浆中 KP/ ANP摩尔比显著低于正常对照组 (P<0 .0 1) ;持续房颤患者血浆中 KP/ ANP摩尔比与正常对照组相似 (P>0 .0 5 )。结论 :KP含量与 ANP比例关系的变化在房颤发病中起一定的作用     

Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.