This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: j.jacc.2007.09.021v1 50/25/2357    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (116) Citing Articles via Google Scholar Google Scholar Articles by Daniels, L. B. Articles by Maisel, A. S. Search for Related Content PubMed PubMed Citation Articles by Daniels, L. B. Articles by Maisel, A. S.

STATE-OF-THE-ART PAPER

Natriuretic Peptides

Division of Cardiology, University of California at San Diego, and the Division of Cardiology, Veteran’s Affairs San Diego Healthcare System, San Diego, California.

Manuscript received July 31, 2007; revised manuscript received September 10, 2007, accepted September 26, 2007.

^_* Reprint requests and correspondence: Dr. Lori B. Daniels, Division of Cardiology, University of California, San Diego, MC 0986, 9350 Campus Point Drive, Suite 1D, La Jolla, California 92037-1300. (Email: loridaniels{at}ucsd.edu).

	Abstract

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

 
Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient’s NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Abbreviations and Acronyms   AF = atrial fibrillation   ANP = atrial natriuretic peptide   AUC = area under the receiver-operating characteristic curve   BNP = B-type natriuretic peptide   CAD = coronary artery disease   CHF = congestive heart failure   ED = emergency department   GFR = glomerular filtration rate   HF = heart failure   LV = left ventricle/ventricular   MI = myocardial infarction   NP = natriuretic peptide   NPR = natriuretic peptide receptor   NTproBNP = amino-terminal fragment of B-type natriuretic peptide   NYHA = New York Heart Association

	The Basics

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

In the setting of volume expansion or pressure overload, the resulting wall stress initiates synthesis of pre–proBNP in the ventricular myocardium. Subsequently, the peptide is cleaved first to proBNP_1-108, then to the biologically active BNP_1-32 and the inactive amino-terminal fragment (NTproBNP). The release of BNP results in improved myocardial relaxation and serves an important regulatory role in response to acute increases in ventricular volume by opposing the vasoconstriction, sodium retention, and antidiuretic effects of the activated renin-angiotensin-aldosterone system (5). The biological actions of NPs are mediated through membrane-bound natriuretic peptide receptors (NPRs) that are linked to a cyclic guanosine monophosphate-dependent signaling cascade, including NPR-A, which preferentially binds ANP and BNP, and NPR-B, which preferentially binds C-type NP. Clearance of NPs from the blood is mediated by NPR-C. In addition, BNP is degraded by neutral endopeptidase, which opens the ring structure and inactivates the peptide. Direct renal filtration and passive excretion might be responsible for some BNP clearance as well.

Circulating forms of NPs in heart failure (HF).   Although blood levels of NPs rise to very high levels in the setting of acute HF, recent studies support the notion that HF patients actually manifest a state of BNP insufficiency, due to both a deficiency of biologically active BNP_1-32 and resistance to its effects (6). Evidence for a state of deficiency comes from molecular analysis of BNP in subjects with acute HF, which reveals 2 distinct circulating forms of BNP: a high-molecular weight form, thought to be proBNP_1-108, and a low-molecular weight form, the 32-amino acid active BNP_1-32 (7). Instead of recognizing BNP_1-32 or NTproBNP alone, recent studies have shown that the standard NP assays also recognize the high-molecular weight proBNP_1-108, which comprises a significant percentage of immunoreactive BNP in HF patients yet seems to have less biologic activity than BNP_1-32, thus explaining the paradox of HF as an NP-deficient state despite high levels of these biomarkers (8,9). Abnormal processing of proBNP into less active forms might also factor into the state of relative BNP insufficiency (10).

In addition, HF patients seem to suffer some degree of BNP resistance. Animal studies have implicated an up-regulation of phosphodiesterase in HF, causing impaired cyclic-GMP activity despite high stimulation of the NPRs by NPs (11). Taken together, these studies help explain the paradox of high measurable BNP and NTproBNP levels in HF patients who nonetheless suffer physiologically from a state of BNP deficiency and its attendant fluid and salt retention.

NTproBNP versus BNP.   Performance characteristics for BNP and NTproBNP are similar in many clinical scenarios. In general, BNP and NTproBNP levels are reasonably correlated, and either can be used in patient care, although clinicians must understand their differences and that absolute levels are not interchangeable (Table 1). The choice of which NP to use often comes down to an institutional decision.

What is a "normal" value?.   The definition of a "normal" NP level depends upon the clinical feature being detected (i.e., severe, symptomatic left ventricular [LV] dysfunction versus subclinical disease) and the prevalence of that condition in the population being tested, because different thresholds will be needed in different clinical settings. In addition, the specific assay used can affect NP levels, particularly when screening the general population, in which NP levels will tend to fall toward the lower end of the spectrum.

Natriuretic peptide levels are clearly age- and gender-specific. Two studies looked at BNP levels in normal subjects without cardiovascular disease or ventricular (systolic or diastolic) dysfunction and found increased levels with age and in women (13,14). Therefore, "normal" values vary.

As a general guideline, in young, healthy adults, 90% will have BNP <25 pg/ml and NTproBNP 70 pg/ml (15). For acutely dyspneic patients, some have suggested cutoffs of BNP <100 pg/ml and NTproBNP <300 pg/ml to rule out HF (Fig. 1) (16,17).

View larger version (24K): [in this window] [in a new window] [Download PPT slide]   Figure 1 BNP Levels by ACC/AHA Heart Failure Stages B-type natriuretic peptide (BNP) rises with age over the course of a lifetime but generally stays under 20 pg/ml in the absence of left ventricular dysfunction or structural heart disease. B-type natriuretic peptide >100 pg/ml is the cutoff for diagnosing congestive heart failure in symptomatic patients. Stage A = risk factors; Stage B = asymptomatic structural heart disease; Stage C = symptomatic heart failure; Stage D = refractory heart failure. ACC = American College of Cardiology; AHA = American Heart Association.

	Diagnosis With NPs

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

The PRIDE (ProBNP Investigation of Dyspnea in the ED) study was a similar study performed with NTproBNP, measured in 600 patients who presented to a single ED with dyspnea. In this study, NTproBNP was sensitive and specific for the diagnosis of congestive heart failure (CHF) (AUC = 0.94). Patients with acute HF had a median NTproBNP over 4,000 pg/ml, compared with 130 pg/ml in those without acute HF. An NTproBNP cut-point of 300 pg/ml was proposed to "rule-out" a diagnosis of HF, whereas higher age-dependent cut-points were suggested to "rule-in" HF (AUC = 0.94) (17).

The cost-effectiveness of using BNP to aid in the emergency diagnosis of HF was shown in the BASEL (BNP for Acute Shortness of breath EvaLuation) study, in which 452 patients presenting to the ED with acute dyspnea were randomized to undergo either a single measurement of BNP or no such measurement (18). Measurement and use of BNP levels by ED physicians was associated with a 10% decrease in the rate of hospital admission and a 3-day decrease in the median length of stay, at a total cost savings of approximately $1,800/patient without increased mortality or repeat hospital stays. Similar improvements in diagnosis and cost savings were seen in the IMPROVE-CHF (Improved Management of Patients With Congestive Heart Failure) study of NTproBNP use in the ED (19).

Diastolic HF
The BNP levels are also useful in establishing a diagnosis of diastolic dysfunction in acute HF patients (20). As diastolic dysfunction increases in severity as assessed by Doppler filling patterns of mitral inflow and pulmonary venous flow, BNP levels rise accordingly (21) as a reflection of LV end-diastolic wall stress (22).

NPs in other clinical scenarios.   Several clinical scenarios exist that can cause NP levels to rise, apart from the typical acute HF setting. Acknowledging these other etiologies for elevated NP levels might help clarify what might otherwise seem to be a discordant clinical picture (Table 2).

Acute Coronary Syndrome
Acute coronary syndrome is associated with a rise in NP levels even in the absence of concomitant HF. The degree of elevation might reflect the severity of LV dysfunction (23). Some have suggested using NP levels as a guide to institute more aggressive treatments aimed at reducing ventricular wall stress (24).

Pulmonary Disease
Differentiating between patients with a pulmonary etiology for their dyspnea and a cardiac etiology can be clinically challenging at times, and the fact that NP levels can be elevated in both settings might confound the picture. However, although patients with pulmonary disease can have elevated NP levels, their elevations often fall within the gray zone and are not usually as high as in patients with CHF (25). Natriuretic peptide levels can still be useful in diagnosing HF in patients with a history of lung disease, such as chronic obstructive pulmonary disease or asthma, because levels will often be higher in patients with both HF and pulmonary disease than in pulmonary disease alone (BNP levels 587 vs. 109 pg/ml, respectively, in the 417 patients from the Breathing Not Properly study with a history of pulmonary disease [asthma or chronic obstructive pulmonary disease] plus a new diagnosis of HF versus those with a history of pulmonary disease without HF) (26).

Elevated NP levels can also be seen in the setting of an acute, hemodynamically significant pulmonary embolism, likely reflecting right heart strain (27). In fact, right heart dysfunction due to severe lung disease from a variety of etiologies can cause elevated NP levels. The mechanism is likely due to release of peptide from the right ventricular myocardium (28), although decreased lung expression of the NPR-C clearance receptor in response to hypoxia has been demonstrated in animal models (29). This scenario can be seen in severe chronic obstructive pulmonary disease, primary pulmonary hypertension, and other causes of pulmonary hypertension (28,30,31). Because of this, when evaluating acutely dyspneic patients, it is important to note that elevated NP levels are not pathognomonic for CHF, and other potentially life-threatening etiologies including pulmonary embolism must still be excluded, especially when NP levels fall within the "gray zone" (BNP 100 to 500 pg/ml; NTproBNP 300 to 900 pg/ml for 50- to 75-year-olds) (32,33).

High-Output States
Several conditions that cause high cardiac outputs, including sepsis, cirrhosis, and hyperthyroidism, can contribute to elevated NP levels. Although the mechanisms are unclear, patients with severe sepsis or shock might have markedly elevated NP levels (34), possibly due to induction by endotoxin or other inflammatory mediators (35) or due to underlying myocardial dysfunction (36). Values are higher in nonsurvivors than in survivors (37). Similarly, hyperthyroid patients might have higher NP levels than euthyroid patients, and although the levels typically do not exceed diagnostic thresholds, they do tend to decrease with treatment of the hyperthyroid state (38). Elevated NP levels are also seen in patients with cirrhosis and likely reflect cardiac dysfunction or a hyperdynamic circulatory state (39).

Atrial Fibrillation (AF)
Natriuretic peptide levels seem to rise in the setting of AF, including lone AF (40). However, in an analysis of the Breathing Not Properly study, Knudsen et al. (41) showed that this pattern was present in patients without but not with HF and that BNP still performed well in patients with AF, with an AUC of 0.84, which was only slightly lower than the AUC of 0.91 for the overall cohort. In patients with AF, a cutoff of 200 pg/ml resulted in a marked improvement in specificity and positive likelihood ratio for diagnosing HF, compared with the conventional cutoff of 100 pg/ml, with little loss of sensitivity.

Caveats: high levels of NPs.   A number of factors have been associated with higher NP levels in addition to ventricular wall stress.

Advanced Age
Both BNP and NTproBNP levels increase with age (14,42), and the increased prevalence of diastolic dysfunction alone does not seem to account for the entire increase. A study by Redfield et al. (13), which excluded patients with "age-related" diastolic dysfunction, nonetheless found an association between age and elevated levels of BNP. Other possible explanations include altered renal function, production, secretion, or metabolism. One study has suggested that there is a reduction in the NPR-C clearance receptor with aging (43).

Female Gender
B-type natriuretic peptide and NTproBNP are higher in women than in men at any age (13,14). Although the reason for the higher levels in women is unknown, estrogen might play a role, because 1 study showed that older women on hormone replacement therapy had higher BNP levels than women not on therapy (13). However, use of estrogen had only a minimal effect on NTproBNP levels in the same community cohort (42), and other data suggest that an inverse relationship between free testosterone levels and NPs and not estrogen levels might be responsible (44).

Renal Disease
The association between NP levels and renal function is complex. Patients with chronic renal dysfunction tend to have higher atrial pressure, systemic pressure, and ventricular mass, all of which could lead to higher "true" physiologic NP levels; or, they might have increased levels due to decreased renal filtration, decreased clearance by NPR-C and endopeptidases within renal tissue, or decreased renal responsiveness to BNP.

Multiple studies have found that BNP levels begin to rise at a threshold of estimated glomerular filtration rate (GFR) of 60 ml/min/1.7 m² (45), which is approximately the same level where increased rates of both systolic and diastolic HF are seen. The NP elevations in patients with chronic renal disease might reflect concurrent LV hypertrophy or coronary disease (46). Because the majority of BNP is not renally cleared, the mechanism of elevated BNP levels in renal failure is likely multifactorial, representing in part a true counter-regulatory response from the heart to the kidney, and not simply decreased passive renal clearance. The Breathing Not Properly study found a weak but significant correlation between GFR and BNP and suggested that higher cut-points are reasonable for those with GFR <60 ml/min/1.7 m² (47).

Clearance of NTproBNP, which is not mediated by the NPR-C receptor or neutral endopeptidase, might be more sensitive than BNP to reduced renal filtration and clearance (48). In a study of breathless patients, there was a stronger relationship between GFR and NTproBNP levels (r = –0.55) than BNP levels, although the relationship was somewhat attenuated among patients with acute CHF (r = –0.33 for NTproBNP and r = –0.18 for BNP) (49). Because of this renal influence, interpretation of NTproBNP levels might be more difficult in patients with a GFR <60 ml/min/1.7 m² (50,51). However, an analysis from the PRIDE study showed that NTproBNP levels in patients with GFR <60 ml/min/1.7 m² were still the strongest independent predictor of outcome and suggested the higher cut-point of NTproBNP >1,200 pg/ml for diagnosing HF in such patients (49). In relatively healthy subjects with only mild renal impairment, in contrast, there seems to be no significant relationship between NTproBNP levels and GFR (42). Thus, NTproBNP might have additional as yet undiscovered modes of clearance, such as degradation by nonspecific peptidases.

Although neither BNP nor NTproBNP are cleared by hemodialysis, BNP levels do rise along with volume status in the days leading up to hemodialysis and then drop by approximately 15% to 30% after a routine hemodialysis session (52).

Caveats: low levels of NPs.   Obesity
Several studies have documented lower BNP levels in obese compared with nonobese patients (14,53–55). This inverse relationship between BMI and BNP has been observed in patients both with and without HF. Although the reason for the relationship is unknown, the increased concentration of the NPR-C clearance receptor on adipocyte cells has led some to postulate that increased clearance is the reason for lower BNP levels in obese patients (56). However, evidence against this hypothesis comes from Das et al. (57), who found that BNP was correlated with greater lean mass but not greater fat mass.

Whether a similar negative correlation is seen with NTproBNP is controversial; some have found that NTproBNP levels might be lower in obese patients, despite the fact that NTproBNP is not believed to be cleared by NPR-C (57,58). Others, however, have found that the degree of impact of body mass index on NTproBNP was minimal (42). A recent study of post-bariatric surgery patients hypothesized that, because both BNP and NTproBNP levels increased after weight loss, decreased NP production and not increased clearance might be the responsible mechanism (59).

Despite the lower circulating levels, NPs retain their prognostic capacity in obese patients (60), although lower NP cut-points are needed for diagnosing HF in patients with a high body mass index (Fig. 2) (55).

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Figure 2 BNP Cut-Points for 90% Sensitivity B-type natriuretic peptide (BNP) cut-points for 90% sensitivity in diagnosing congestive heart failure in patients with dyspnea, on the basis of body mass index (BMI) subgroup. Specificity at the 90% sensitivity level shown was at least 70% for all 3 groups. Data from the Breathing Not Properly Multinational Study; figure adapted from Daniels et al. (55).

CHF Due to Causes Upstream From the LV
When CHF is due to a cause upstream from the LV—as in acute mitral regurgitation or mitral stenosis, for example—NP levels might be relatively low despite impressive symptoms. The absence of significant LV wall stress in these acute settings explains the lack of marked BNP production, and although NP levels might still be higher than normal, they will not rise to the same degree as when the CHF occurs with a concomitant overload on the LV. Similarly, pericardial constriction can sometimes cause symptoms of CHF; however, because the myocardium is prevented from stretching by the confines of the pericardium, NP levels are typically normal or only minimally elevated in this setting (61).

	Prognosis

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

 
Evidence continues to mount showing that NP levels measured in various settings are highly predictive of subsequent cardiac events (Table 3) (62–70).

In chronic HF patients too, NP levels provide powerful prognostic information about survival and are predictors of functional status deterioration (73,74). In an evaluation of Val-HeFT (Valsartan Heart Failure Trial) comprising 4,300 outpatients with chronic HF, those with the greatest increase in BNP despite therapy had the highest morbidity and mortality (74).

Coronary artery disease (CAD)/acute coronary syndrome/sudden cardiac death.   Stable Angina
Both BNP and NTproBNP have strong prognostic value in patients with stable CAD and display nearly identical test performance in predicting all-cause mortality or HF (75). In a study of 1,085 patients with stable CAD followed for an average of 2.5 years, BNP and LV ejection fraction were the strongest predictors of future cardiovascular events, independent of known risk factors. B-type natriuretic peptide had the highest prognostic accuracy and was complementary to the angiographically defined extent of CAD and to LV systolic function (76). Similar prognostic utility has been demonstrated for NTproBNP, which improved prediction of all-cause mortality above and beyond the predictive ability from conventional cardiovascular risk factors (77,78).

Unstable Angina and MI
Natriuretic peptide levels obtained in patients with unstable angina and MI also play a prognostic role, which is incremental and in some instances superior to the prognostic value of troponins (79–82). Persistent elevation of NTproBNP 3 to 6 months after an acute coronary syndrome is associated with chronically impaired LV function (80). Some have recommended, on the basis of these data, careful re-evaluation for risk-reducing interventions when NP levels remain elevated 3 months after an acute coronary syndrome (83).

Sudden Cardiac Death
Several studies have shown that NPs might be useful in predicting who is at risk for sudden cardiac death (73,84). In 452 ambulatory patients with HF and LV ejection fraction <35%, BNP levels independently predicted sudden cardiac death (73). In this study, only 1% of patients with BNP <130 pg/ml died suddenly, compared with 19% of patients with BNP 130 pg/ml. Natriuretic peptides might help predict sudden cardiac death after acute MI as well. A study of 521 acute MI patients found that BNP predicted sudden cardiac death (but not other deaths) and was the strongest predictor even after adjusting for clinical variables, including ejection fraction (84).

In cardiomyopathy patients undergoing cardioverter-defibrillator implantation, a single pre-implantation BNP level is independently predictive of future appropriate defibrillator therapies (85). Although decisions to implant a defibrillator should not be made solely on the basis of NP levels, future research might find that NP levels can help guide our choices more wisely.

Cardiac Resynchronization Therapy
In patients with New York Heart Association (NYHA) functional class III or IV HF, BNP 447 pg/ml can help predict cardiac resynchronization therapy response at 6 months, defined as absence of hospital stays for HF and improvement by at least 1 NYHA functional class (86). Cardiac resynchronization therapy induces an early and sustained reduction in NP levels, which might reflect the efficacy of the therapy (87). Future large studies will determine whether NP levels are helpful in targeting candidates for cardiac resynchronization and for monitoring those already with the devices.

Valvular disease.   In the setting of cardiac valvular disorders, NPs are becoming a useful clinical tool for monitoring patients’ pre- and post-valvular surgery. In general, NP levels tend to rise with increasing severity of the valvular abnormality and with the resulting cardiac remodeling. Natriuretic peptide levels can also provide important prognostic information and might assist with risk stratification and timing for surgery.

Mitral Valve
Natriuretic peptide levels increase with increasing severity of mitral regurgitation (88). Recently, BNP was shown to be a marker of poor outcome in a study of 124 patients with organic mitral regurgitation, where levels were independently predictive of death (89).

Owing to underfilling of the LV, NP levels might not rise as high in mitral stenosis as they might in other causes of HF; however, NP levels do increase in this setting and decrease after balloon valvotomy (90). Natriuretic peptide levels are correlated with echocardiographic findings, including mitral valve area and mean mitral gradient, as well as NYHA functional class (91).

Aortic Valve
In the setting of aortic stenosis, NP levels are associated with severity of stenosis, might predict development of symptom onset, and increase progressively with worsening NYHA functional class (92). Levels might also predict survival in patients with stenosis who are treated without surgery (93). In patients who do undergo valve replacement, NP levels might predict survival and post-operative LV function (94).

In chronic aortic regurgitation, NP levels are also associated with severity of regurgitation even in asymptomatic individuals (95), although levels tend to rise less than in aortic stenosis even when LV dilation has occurred. Thus, measurement of NP levels might complement clinical and echocardiographic evaluation, particularly when symptoms are unclear or when valvular function is difficult to interpret on echocardiography.

Cardiac and vascular surgery.   Natriuretic peptide levels measured pre-operatively can help predict post-operative outcomes such as mortality and major adverse cardiac events among patients undergoing cardiac or vascular surgery (96,97). Levels can also help predict which patients are at increased risk of developing post-operative AF (98).

Pulmonary embolism.   Patients with pulmonary embolism and other pulmonary diseases can also have elevated levels of NPs, although not usually to the same extent as in CHF. In the setting of acute pulmonary embolism, BNP levels <50 pg/ml or NTproBNP levels <500 pg/ml might help predict a benign outcome (27,99), although some have suggested lower cut-points for improved negative predictive values.

	Monitoring Therapy

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

 
Because NP levels fluctuate with changes in myocardial filling pressures, monitoring levels might be helpful in evaluating the progress of patients receiving therapies aimed at reducing this wall stress.

Biologic variability of NP levels.   Several studies have shown considerable intraindividual variation of NP levels in both normal individuals and in apparently stable HF patients (100,101). These studies suggest that serial BNP levels need to change by a minimum of approximately 70% to constitute a significant change over 1 week in stable HF patients and NTproBNP levels must change by at least 50% (100,101). The degree of biologic variability in acutely decompensated patients is more difficult to ascertain, but in general, because clinical improvement should be associated with large changes in NP levels, the degree of intraindividual variability might be less important than in the outpatient arena of stable patients.

Inpatients.   Several studies have evaluated the relationship between NP levels and pulmonary capillary wedge pressure measurements derived from invasive hemodynamic catheters. Not all patients with elevated NP levels will have high wedge pressures; as detailed earlier, there are many clinical situations in which NP levels can seem discordant with the clinical picture. Thus, in a given patient, the NP level does not always correlate to wedge pressure (102). However, in patients with decompensated HF due to volume overload, a treatment-induced drop in wedge pressure will almost always be accompanied by a rapid drop in NP levels, especially during the first 24 h of treatment, as long as adequate urine output is maintained (103).

In patients with decompensated HF, the NP level can hypothetically be thought of as consisting of 2 components: the "dry weight" component, which reflects the patient’s compensated NP level, plus the additional NP level due to the acute pressure or volume overload.

Natriuretic peptide levels do not need to be measured each hospital day; however, the failure of NP levels to decrease during hospital stay is a poor prognostic sign (104,105). More important than repeated measurements of NP levels in inpatients is obtaining a level immediately before discharge. A single pre-discharge BNP level is strongly predictive of early and later outcome, regardless of the initial BNP level or echocardiographic findings (106). In a study of 114 patients admitted with CHF, those with a pre-discharge BNP level >700 pg/ml were over 15 times more likely to die or get readmitted within 6 months compared with those with BNP <350 pg/ml at discharge (107).

A reasonable approach to monitoring inpatients with decompensated HF would be to obtain an NP level on admission and just before discharge when the patient is presumed to be euvolemic, both for prognostic purposes and to aid in tailoring the intensity of post-discharge care (108); it might also help to establish the patient’s "dry weight" NP level, although patients often need additional diuresis after discharge, leading ultimately to a dry weight NP level lower than the discharge level. Additional measurement of NP levels in inpatients might be appropriate if the patient experiences a significant change in status during the hospital stay, although the benefit of this has not been tested.

Outpatients.   Monitoring NP levels in the outpatient setting might improve patient care and outcomes, although prospective studies of this have shown conflicting results. In the STARS-BNP (Systolic Heart Failure Treatment Supported by BNP) study of 220 patients with HF and LV dysfunction who were randomized to receive therapy guided by NP levels or standard care, NP-guided treatment targeting a BNP level <100 pg/ml significantly reduced HF deaths and hospital stays for HF (109). However, the smaller STARBRITE (Strategies for Tailoring Advanced Heart Failure Regimens in the Outpatient Setting: BRain NatrIuretic Peptide Versus the Clinical CongesTion ScorE) study (n = 130) failed to show a significant improvement in the primary outcome of nonhospital days alive in patients whose treatment was guided by BNP levels, although STARBRITE enrolled sicker patients and used a higher BNP target than STARS-BNP (110). In both STARS-BNP and STARBRITE, clinicians who adjusted treatments based on BNP levels prescribed higher doses of angiotensin-converting enzyme (ACE) inhibitors and beta blockers, compared with those whose treatment was guided by clinical signs and symptoms alone.

For patients regularly followed in clinic, it might be beneficial to establish their "steady state" NP level, that is, the BNP or NTproBNP level that corresponds to their optimized fluid status. Knowing a patient’s steady state NP level might be helpful for management in both the inpatient and outpatient settings, because baseline NP levels can vary on the basis of the patient’s underlying severity of disease and NYHA functional class (111). Significant deviations above this steady state value might prove more helpful than traditional cut-points for diagnosing HF exacerbations in those individuals who are closely followed as outpatients and whose NP levels tend to stay elevated, whereas values much lower than their steady state level might signal a patient who is over-diuresed or intravascularly depleted.

A post-discharge rise in NP level can be an important marker for repeat hospital stay. How high an NP level must rise over baseline before a patient is deemed "decompensated" is unknown, because as noted previously, there is a certain amount of intraindividual variation in NP levels, and certainly the clinical picture is important in this regard. However, an increase by at least 50% over one’s steady state NP level might be a reasonable benchmark for triggering an evaluation for confirmatory signs and symptoms followed by more aggressive treatment.

	Toward the Future—Screening for Subclinical Disease

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

 
Up to one-half of individuals with LV dysfunction might be asymptomatic and unaware of their condition (112,113). Because NPs are elevated in the setting of LV dysfunction, their use as a screening test for this condition has aroused much interest. Although echocardiography is the current gold standard for detection of LV dysfunction and many other structural cardiac abnormalities, its cost and limited availability make it an impractical choice for mass screening.

Several studies have evaluated the use of NPs to identify asymptomatic subjects with poor ventricular function. Most concluded that, owing to the relatively low prevalence of disease, the best potential use for NPs was to use the high negative predictive value for "ruling out" disease (114,115). Other studies looking to screen for a broader range of subclinical cardiovascular disorders also found excellent negative predictive value (116).

The diagnostic value of NPs in community screening depends largely on the prevalence of disease. As such, NPs might be most useful for detecting a range of clinical disorders. In the Framingham Offspring Study of 3,346 asymptomatic middle-age subjects, for example, Wang et al. (117) prospectively examined BNP and NT-proANP levels and found that BNP levels were independently predictive of the risk of death, HF, stroke or transient ischemic attack, and AF, even after adjusting for traditional risk factors. The BNP levels above the 80th percentile (approximately 20 pg/ml) carried a 62% increased risk of death and a 76% increased risk of a first major cardiovascular event. With each increment of 1 SD in log BNP levels, there was a 27% increase in risk of death, a 77% increase in risk of HF, a 66% increase in the risk of AF, and a 53% increase in the risk of stroke or transient ischemic attack, all of which were statistically significant. Another study in nonhospitalized individuals ages 50 to 89 years showed that NTproBNP provides prognostic information of mortality and first major cardiovascular events beyond traditional risk factors (118). Thus even small elevations of NP levels (e.g., in the BNP 20- to 100-pg/ml range), significantly less than traditional cut-points for acutely dyspneic patients, might serve as an early warning sign, aiding in the timely detection of cardiovascular disease.

An intriguing future use of NPs might be as an adjunct to the athletic pre-participation screening exam. A preliminary study of college athletes showed that most have low levels of NPs (15); on the basis of what is known about NPs, athletes with the highest NP levels might have a physiologic basis for the elevation and might represent a higher-risk subgroup that warrants closer evaluation. However, large-scale studies are needed to evaluate the incremental value and cost-effectiveness of using NPs in this setting.

Cost-effectiveness.   Screening populations at high risk for development of HF, such as diabetic and elderly patients, and referring those with elevated NP levels for echocardiogram might in fact prove cost-effective despite the higher prevalence of elevated NP levels in these populations (119,120). Heidenreich et al. (120) recently found that using a BNP cutoff level of 24 pg/ml for echocardiogram referral was a cost-effective means of screening for LV dysfunction in populations (such as men over age 60 years and possibly women over age 60 years) with a prevalence of LV systolic dysfunction of at least 1%.

	Footnotes

 
This work is supported in part by a Western States Affiliate Post-Doctoral Award from the American Heart Association (to Dr. Daniels). Dr. Daniels has received research funding from Roche. Dr. Maisel has received research funding from Bayer, Abbott, and Roche and has served as a paid consultant for Biosite. James de Lemos, MD, served as Guest Editor for this article.

	References

Top Abstract The Basics Diagnosis With NPs Prognosis Monitoring Therapy Toward the Future--Screening for... References

 
1. Nakao K, Ogawa Y, Suga S, Imura H. Molecular biology and biochemistry of the natriuretic peptide systemII: natriuretic peptide receptors. J Hypertens 1992;10:1111-1114.[CrossRef][Web of Science][Medline]

2. Yasue H, Yoshimura M, Sumida H, et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure Circulation 1994;90:195-203.[Abstract/Free Full Text]

3. Yoshimura M, Yasue H, Okumura K, et al. Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure Circulation 1993;87:464-469.[Abstract/Free Full Text]

4. Soeki T, Kishimoto I, Okumura H, et al. C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction J Am Coll Cardiol 2005;45:608-616.[Abstract/Free Full Text]

5. Nakagawa O, Ogawa Y, Itoh H, et al. Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophyEvidence for brain natriuretic peptide as an "emergency" cardiac hormone against ventricular overload. J Clin Invest 1995;96:1280-1287.[Web of Science][Medline]

6. Chen HH. Heart failure: a state of brain natriuretic peptide deficiency or resistance or both! J Am Coll Cardiol 2007;49:1089-1091.[Free Full Text]

7. Shimizu H, Masuta K, Aono K, et al. Molecular forms of human brain natriuretic peptide in plasma Clin Chim Acta 2002;316:129-135.[CrossRef][Web of Science][Medline]

8. Liang F, O’Rear J, Schellenberger U, et al. Evidence for functional heterogeneity of circulating B-type natriuretic peptide J Am Coll Cardiol 2007;49:1071-1078.[Abstract/Free Full Text]

9. Hawkridge AM, Heublein DM, Bergen 3rd HR, Cataliotti A, Burnett Jr. JC, Muddiman DC. Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure Proc Natl Acad Sci U S A 2005;102:17442-17447.[Abstract/Free Full Text]

10. Lam CS, Burnett Jr. JC, Costello-Boerrigter L, Rodeheffer RJ, Redfield MM. Alternate circulating pro-B-type natriuretic peptide and B-type natriuretic peptide forms in the general population J Am Coll Cardiol 2007;49:1193-1202.[Abstract/Free Full Text]

11. Forfia PR, Lee M, Tunin RS, Mahmud M, Champion HC, Kass DA. Acute phosphodiesterase 5 inhibition mimics hemodynamic effects of B-type natriuretic peptide and potentiates B-type natriuretic peptide effects in failing but not normal canine heart J Am Coll Cardiol 2007;49:1079-1088.[Abstract/Free Full Text]

12. Vickery S, Price CP, John RI, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy Am J Kidney Dis 2005;46:610-620.[CrossRef][Web of Science][Medline]

13. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett Jr JC. Plasma brain natriuretic peptide concentration: impact of age and gender J Am Coll Cardiol 2002;40:976-982.[Abstract/Free Full Text]

14. Wang TJ, Larson MG, Levy D, et al. Impact of age and sex on plasma natriuretic peptide levels in healthy adults Am J Cardiol 2002;90:254-258.[CrossRef][Web of Science][Medline]

15. Daniels LB, Allison MA, Clopton P, et al. Use of natriuretic peptides in pre-participation screening of college athletes Int J Cardiol 2007Mar 27;[E-pub ahead of print].

16. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure N Engl J Med 2002;347:161-167.[CrossRef][Web of Science][Medline]

17. Januzzi Jr. JL, Camargo CA, Anwaruddin S, et al. The N-terminal pro-BNP investigation of dyspnea in the emergency department (PRIDE) study Am J Cardiol 2005;95:948-954.[CrossRef][Web of Science][Medline]

18. Mueller C, Scholer A, Laule-Kilian K, et al. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea N Engl J Med 2004;350:647-654.[CrossRef][Web of Science][Medline]

19. Moe GW, Howlett J, Januzzi JL, Zowall H. N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVE-CHF study Circulation 2007;115:3103-3110.[Abstract/Free Full Text]

20. Yamaguchi H, Yoshida J, Yamamoto K, et al. Elevation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricular hypertrophy J Am Coll Cardiol 2004;43:55-60.[Abstract/Free Full Text]

21. Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings Circulation 2002;105:595-601.[Abstract/Free Full Text]

22. Iwanaga Y, Nishi I, Furuichi S, et al. B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure J Am Coll Cardiol 2006;47:742-748.[Abstract/Free Full Text]

23. Morita E, Yasue H, Yoshimura M, et al. Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction Circulation 1993;88:82-91.[Abstract/Free Full Text]

24. Giugliano RP, Braunwald E. The year in non–ST-segment elevation acute coronary syndromes J Am Coll Cardiol 2006;48:386-395.[Free Full Text]

25. Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A. Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea J Am Coll Cardiol 2002;39:202-209.[Abstract/Free Full Text]

26. McCullough PA, Hollander JE, Nowak RM, et al. Uncovering heart failure in patients with a history of pulmonary disease: rationale for the early use of B-type natriuretic peptide in the emergency department Acad Emerg Med 2003;10:198-204.[CrossRef][Web of Science][Medline]

27. Kucher N, Printzen G, Goldhaber SZ. Prognostic role of brain natriuretic peptide in acute pulmonary embolism Circulation 2003;107:2545-2547.[Abstract/Free Full Text]

28. Nagaya N, Nishikimi T, Okano Y, et al. Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension J Am Coll Cardiol 1998;31:202-208.[Abstract/Free Full Text]

29. Klinger JR, Arnal F, Warburton RR, Ou LC, Hill NS. Downregulation of pulmonary atrial natriuretic peptide receptors in rats exposed to chronic hypoxia J Appl Physiol 1994;77:1309-1316.[Abstract/Free Full Text]

30. Bando M, Ishii Y, Sugiyama Y, Kitamura S. Elevated plasma brain natriuretic peptide levels in chronic respiratory failure with cor pulmonale Respir Med 1999;93:507-514.[CrossRef][Web of Science][Medline]

31. Nagaya N, Nishikimi T, Uematsu M, et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension Circulation 2000;102:865-870.[Abstract/Free Full Text]

32. Brenden CK, Hollander JE, Guss D, et al. Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study Am Heart J 2006;151:1006-1011.[CrossRef][Web of Science][Medline]

33. van Kimmenade RR, Pinto YM, Bayes-Genis A, Lainchbury JG, Richards AM, Januzzi Jr JL. Usefulness of intermediate amino-terminal pro-brain natriuretic peptide concentrations for diagnosis and prognosis of acute heart failure Am J Cardiol 2006;98:386-390.[CrossRef][Web of Science][Medline]

34. Rudiger A, Gasser S, Fischler M, Hornemann T, von Eckardstein A, Maggiorini M. Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure Crit Care Med 2006;34:2140-2144.[CrossRef][Web of Science][Medline]

35. Ma KK, Ogawa T, de Bold AJ. Selective upregulation of cardiac brain natriuretic peptide at the transcriptional and translational levels by pro-inflammatory cytokines and by conditioned medium derived from mixed lymphocyte reactions via p38 MAP kinase J Mol Cell Cardiol 2004;36:505-513.[CrossRef][Web of Science][Medline]

36. Charpentier J, Luyt CE, Fulla Y, et al. Brain natriuretic peptide: a marker of myocardial dysfunction and prognosis during severe sepsis Crit Care Med 2004;32:660-665.[CrossRef][Web of Science][Medline]

37. Varpula M, Pulkki K, Karlsson S, Ruokonen E, Pettila V, FINNSEPSIS Study Group Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock Crit Care Med 2007;35:1277-1283.[CrossRef][Web of Science][Medline]

38. Schultz M, Faber J, Kistorp C, et al. N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) in different thyroid function states Clin Endocrinol (Oxf) 2004;60:54-59.[CrossRef][Medline]

39. Yildiz R, Yildirim B, Karincaoglu M, Harputluoglu M, Hilmioglu F. Brain natriuretic peptide and severity of disease in non-alcoholic cirrhotic patients J Gastroenterol Hepatol 2005;20:1115-1120.[Web of Science][Medline]

40. Ellinor PT, Low AF, Patton KK, Shea MA, Macrae CA. Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation J Am Coll Cardiol 2005;45:82-86.[Abstract/Free Full Text]

41. Knudsen CW, Omland T, Clopton P, et al. Impact of atrial fibrillation on the diagnostic performance of B-type natriuretic peptide concentration in dyspneic patients: an analysis from the Breathing Not Properly Multinational Study J Am Coll Cardiol 2005;46:838-844.[Abstract/Free Full Text]

42. Costello-Boerrigter LC, Boerrigter G, Redfield MM, et al. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction J Am Coll Cardiol 2006;47:345-353.[Abstract/Free Full Text]

43. Kawai K, Hata K, Tanaka K, et al. Attenuation of biologic compensatory action of cardiac natriuretic peptide system with aging Am J Cardiol 2004;93:719-723.[CrossRef][Web of Science][Medline]

44. Chang AY, Abdullah SM, Jain T, et al. Associations among androgens, estrogens, and natriuretic peptides in young women: observations from the Dallas Heart Study J Am Coll Cardiol 2007;49:109-116.[Abstract/Free Full Text]

45. Tsutamoto T, Wada A, Sakai H, et al. Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure J Am Coll Cardiol 2006;47:582-586.[Abstract/Free Full Text]

46. DeFilippi CR, Fink JC, Nass CM, Chen H, Christenson R. N-terminal pro-B-type natriuretic peptide for predicting coronary disease and left ventricular hypertrophy in asymptomatic CKD not requiring dialysis Am J Kidney Dis 2005;46:35-44.[CrossRef][Web of Science][Medline]

47. McCullough PA, Duc P, Omland T, et al. B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study Am J Kidney Dis 2003;41:571-579.[CrossRef][Web of Science][Medline]

48. Lamb EJ, Vickery S, Price CP. Amino-terminal pro-brain natriuretic peptide to diagnose congestive heart failure in patients with impaired kidney function J Am Coll Cardiol 2006;48:1060-1061.[Free Full Text]

49. Anwaruddin S, Lloyd-Jones DM, Baggish A, et al. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study J Am Coll Cardiol 2006;47:91-97.[Abstract/Free Full Text]

50. Roche DiagnosticsElecsys proBNP package insert. Indianapolis, IN: Roche Diagnostics; 2003.

51. Richards AM, Nicholls MG, Yandle TG, et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction Circulation 1998;97:1921-1929.[Abstract/Free Full Text]

52. Haug C, Metzele A, Steffgen J, Grunert A. Changes in brain natriuretic peptide and atrial natriuretic peptide plasma concentrations during hemodialysis in patients with chronic renal failure Horm Metab Res 1994;26:246-249.[Web of Science][Medline]

53. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure J Am Coll Cardiol 2004;43:1590-1595.[Abstract/Free Full Text]

54. Wang TJ, Larson MG, Levy D, et al. Impact of obesity on plasma natriuretic peptide levels Circulation 2004;109:594-600.[Abstract/Free Full Text]

55. Daniels LB, Clopton P, Bhalla V, et al. How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failureResults from the Breathing Not Properly Multinational Study. Am Heart J 2006;151:999-1005.[CrossRef][Web of Science][Medline]

56. Sarzani R, Dessi-Fulgheri P, Paci VM, Espinosa E, Rappelli A. Expression of natriuretic peptide receptors in human adipose and other tissues J Endocrinol Invest 1996;19:581-585.[Web of Science][Medline]

57. Das SR, Drazner MH, Dries DL, et al. Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study Circulation 2005;112:2163-2168.[Abstract/Free Full Text]

58. Krauser DG, Lloyd-Jones DM, Chae CU, et al. Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy Am Heart J 2005;149:744-750.[CrossRef][Web of Science][Medline]

59. van Kimmenade R, van Dielen F, Bakker J, et al. Is brain natriuretic peptide production decreased in obese subjects? J Am Coll Cardiol 2006;47:886-887.[Free Full Text]

60. Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic peptide levels in obese patients with advanced heart failure J Am Coll Cardiol 2006;47:85-90.[Abstract/Free Full Text]

61. Leya FS, Arab D, Joyal D, et al. The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy J Am Coll Cardiol 2005;45:1900-1902.[Abstract/Free Full Text]

62. Fonarow GC, Peacock WF, Phillips CO, Givertz MM, Lopatin M. Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure J Am Coll Cardiol 2007;49:1943-1950.[Abstract/Free Full Text]

63. Januzzi JL, van Kimmenade R, Lainchbury J, et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study Eur Heart J 2006;27:330-337.[Abstract/Free Full Text]

64. Hartmann F, Packer M, Coats AJ, et al. Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial Circulation 2004;110:1780-1786.[Abstract/Free Full Text]

65. Morrow DA, de Lemos JA, Blazing MA, et al. Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease JAMA 2005;294:2866-2871.[Abstract/Free Full Text]

66. Fijalkowska A, Kurzyna M, Torbicki A, et al. Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension Chest 2006;129:1313-1321.[CrossRef][Web of Science][Medline]

67. Zoccali C, Mallamaci F, Benedetto FA, et al. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients J Am Soc Nephrol 2001;12:1508-1515.[Abstract/Free Full Text]

68. Rienstra M, Van Gelder IC, Van den Berg MP, Boomsma F, Van Veldhuisen DJ. Natriuretic peptides in patients with atrial fibrillation and advanced chronic heart failure: determinants and prognostic value of (NT-)ANP and (NT-pro)BNP Europace 2006;8:482-487.[Abstract/Free Full Text]

69. Jensen JK, Mickley H, Bak S, Korsholm L, Kristensen SR. Serial measurements of N-terminal pro-brain natriuretic peptide after acute ischemic stroke Cerebrovasc Dis 2006;22:439-444.[Web of Science][Medline]

70. Ueda S, Nishio K, Akai Y, et al. Prognostic value of increased plasma levels of brain natriuretic peptide in patients with septic shock Shock 2006;26:134-139.[CrossRef][Web of Science][Medline]

71. Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review BMJ 2005;330:625.[Abstract/Free Full Text]

72. Maisel A, Hollander JE, Guss D, et al. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT)A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol 2004;44:1328-1333.[Abstract/Free Full Text]

73. Berger R, Huelsman M, Strecker K, et al. B-type natriuretic peptide predicts sudden death in patients with chronic heart failure Circulation 2002;105:2392-2397.[Abstract/Free Full Text]

74. Anand IS, Fisher LD, Chiang YT, et al. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT) Circulation 2003;107:1278-1283.[Abstract/Free Full Text]

75. Richards M, Nicholls MG, Espiner EA, et al. Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease J Am Coll Cardiol 2006;47:52-60.[Abstract/Free Full Text]

76. Schnabel R, Lubos E, Rupprecht HJ, et al. B-type natriuretic peptide and the risk of cardiovascular events and death in patients with stable angina: results from the AtheroGene study J Am Coll Cardiol 2006;47:552-558.[Abstract/Free Full Text]

77. Kragelund C, Gronning B, Kober L, Hildebrandt P, Steffensen R. N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease N Engl J Med 2005;352:666-675.[CrossRef][Web of Science][Medline]

78. Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA. N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease JAMA 2007;297:169-176.[Abstract/Free Full Text]

79. de Lemos JA, Morrow DA, Bentley JH, et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes N Engl J Med 2001;345:1014-1021.[CrossRef][Web of Science][Medline]

80. Lindahl B, Lindback J, Jernberg T, et al. Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy J Am Coll Cardiol 2005;45:533-541.[Abstract/Free Full Text]

81. Kwan G, Isakson SR, Beede J, Clopton P, Maisel AS, Fitzgerald RL. Short-term serial sampling of natriuretic peptides in patients presenting with chest pain J Am Coll Cardiol 2007;49:1186-1192.[Abstract/Free Full Text]

82. James SK, Lindback J, Tilly J, et al. Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes: a GUSTO-IV substudy J Am Coll Cardiol 2006;48:1146-1154.[Abstract/Free Full Text]

83. Mills RM. Warning! Context-sensitive data J Am Coll Cardiol 2005;45:542-543.[Free Full Text]

84. Tapanainen JM, Lindgren KS, Makikallio TH, Vuolteenaho O, Leppaluoto J, Huikuri HV. Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era J Am Coll Cardiol 2004;43:757-763.[Abstract/Free Full Text]

85. Verma A, Kilicaslan F, Martin DO, et al. Preimplantation B-type natriuretic peptide concentration is an independent predictor of future appropriate implantable defibrillator therapies Heart 2006;92:190-195.[Abstract/Free Full Text]

86. Lellouche N, De Diego C, Cesario DA, et al. Usefulness of preimplantation B-type natriuretic peptide level for predicting response to cardiac resynchronization therapy Am J Cardiol 2007;99:242-246.[CrossRef][Web of Science][Medline]

87. Fruhwald FM, Fahrleitner-Pammer A, Berger R, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony Eur Heart J 2007;28:1592-1597.[Abstract/Free Full Text]

88. Sutton TM, Stewart RA, Gerber IL, et al. Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation J Am Coll Cardiol 2003;41:2280-2287.[Abstract/Free Full Text]

89. Detaint D, Messika-Zeitoun D, Avierinos JF, et al. B-type natriuretic peptide in organic mitral regurgitation: determinants and impact on outcome Circulation 2005;111:2391-2397.[Abstract/Free Full Text]

90. Tharaux PL, Dussaule JC, Hubert-Brierre J, Vahanian A, Acar J, Ardaillou R. Plasma atrial and brain natriuretic peptides in mitral stenosis treated by valvulotomy Clin Sci (Lond) 1994;87:671-677.[Medline]

91. Arat-Ozkan A, Kaya A, Yigit Z, et al. Serum N-terminal pro-BNP levels correlate with symptoms and echocardiographic findings in patients with mitral stenosis Echocardiography 2005;22:473-478.[CrossRef][Web of Science][Medline]

92. Gerber IL, Stewart RA, Legget ME, et al. Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis Circulation 2003;107:1884-1890.[Abstract/Free Full Text]

93. Nessmith MG, Fukuta H, Brucks S, Little WC. Usefulness of an elevated B-type natriuretic peptide in predicting survival in patients with aortic stenosis treated without surgery Am J Cardiol 2005;96:1445-1448.[CrossRef][Web of Science][Medline]

94. Bergler-Klein J, Klaar U, Heger M, et al. Natriuretic peptides predict symptom-free survival and post-operative outcome in severe aortic stenosis Circulation 2004;109:2302-2308.[Abstract/Free Full Text]

95. Gerber IL, Stewart RA, French JK, et al. Associations between plasma natriuretic peptide levels, symptoms, and left ventricular function in patients with chronic aortic regurgitation Am J Cardiol 2003;92:755-758.[CrossRef][Web of Science][Medline]

96. Hutfless R, Kazanegra R, Madani M, et al. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery J Am Coll Cardiol 2004;43:1873-1879.[Abstract/Free Full Text]

97. Feringa HH, Schouten O, Dunkelgrun M, et al. Plasma N-terminal pro-B-type natriuretic peptide as long-term prognostic marker after major vascular surgery Heart 2007;93:226-231.[Abstract/Free Full Text]

98. Wazni OM, Martin DO, Marrouche NF, et al. Plasma B-type natriuretic peptide levels predict postoperative atrial fibrillation in patients undergoing cardiac surgery Circulation 2004;110:124-127.[Abstract/Free Full Text]

99. Kucher N, Printzen G, Doernhoefer T, Windecker S, Meier B, Hess OM. Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism Circulation 2003;107:1576-1578.[Abstract/Free Full Text]

100. O’Hanlon R, O’Shea P, Ledwidge M, et al. The biologic variability of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in stable heart failure patients J Card Fail 2007;13:50-55.[CrossRef][Web of Science][Medline]

101. Wu AH, Smith A, Wieczorek S, et al. Biological variation for N-terminal pro- and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure Am J Cardiol 2003;92:628-631.[CrossRef][Web of Science][Medline]

102. Forfia PR, Watkins SP, Rame JE, Stewart KJ, Shapiro EP. Relationship between B-type natriuretic peptides and pulmonary capillary wedge pressure in the intensive care unit J Am Coll Cardiol 2005;45:1667-1671.[Abstract/Free Full Text]

103. Kazanegra R, Cheng V, Garcia A, et al. A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study J Card Fail 2001;7:21-29.[CrossRef][Web of Science][Medline]

104. Cheng V, Kazanagra R, Garcia A, et al. A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study J Am Coll Cardiol 2001;37:386-391.[Abstract/Free Full Text]

105. Bettencourt P, Ferreira S, Azevedo A, Ferreira A. Preliminary data on the potential usefulness of B-type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure Am J Med 2002;113:215-219.[CrossRef][Web of Science][Medline]

106. Dokainish H, Zoghbi WA, Lakkis NM, et al. Incremental predictive power of B-type natriuretic peptide and tissue Doppler echocardiography in the prognosis of patients with congestive heart failure J Am Coll Cardiol 2005;45:1223-1226.[Abstract/Free Full Text]

107. Logeart D, Thabut G, Jourdain P, et al. Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure J Am Coll Cardiol 2004;43:635-641.[Abstract/Free Full Text]

108. Maisel A. The coming of age of natriuretic peptides: the emperor does have clothes! J Am Coll Cardiol 2006;47:61-64.[Free Full Text]

109. Jourdain P, Jondeau G, Funck F, et al. Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP multicenter study J Am Coll Cardiol 2007;49:1733-1739.[Abstract/Free Full Text]

110. Shah MR, Califf RM, Nohria A, et al. STARBRITE: a randomized pilot trial of BNP-guided therapy in patients with advanced heart failure. Paper presented at: American Heart Association Scientific Sessions; November 12–15, 2006; Chicago, IL.

111. Lee SC, Stevens TL, Sandberg SM, et al. The potential of brain natriuretic peptide as a biomarker for New York Heart Association class during the outpatient treatment of heart failure J Card Fail 2002;8:149-154.[CrossRef][Web of Science][Medline]

112. McDonagh TA, Morrison CE, Lawrence A, et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population Lancet 1997;350:829-833.[CrossRef][Web of Science][Medline]

113. Redfield MM, Jacobsen SJ, Burnett Jr. JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic JAMA 2003;289:194-202.[Abstract/Free Full Text]

114. McDonagh TA, Robb SD, Murdoch DR, et al. Biochemical detection of left-ventricular systolic dysfunction Lancet 1998;351:9-13.[CrossRef][Web of Science][Medline]

115. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett Jr JC. Plasma brain natriuretic peptide to detect preclinical ventricular systolic or diastolic dysfunction: a community-based study Circulation 2004;109:3176-3181.[Abstract/Free Full Text]

116. Nakamura M, Endo H, Nasu M, Arakawa N, Segawa T, Hiramori K. Value of plasma B type natriuretic peptide measurement for heart disease screening in a Japanese population Heart 2002;87:131-135.[Abstract/Free Full Text]

117. Wang TJ, Larson MG, Levy D, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death N Engl J Med 2004;350:655-663.[CrossRef][Web of Science][Medline]

118. Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults JAMA 2005;293:1609-1616.[Abstract/Free Full Text]

119. Baker DW, Bahler RC, Finkelhor RS, Lauer MS. Screening for left ventricular systolic dysfunction among patients with risk factors for heart failure Am Heart J 2003;146:736-740.[CrossRef][Web of Science][Medline]

120. Heidenreich PA, Gubens MA, Fonarow GC, Konstam MA, Stevenson LW, Shekelle PG. Cost-effectiveness of screening with B-type natriuretic peptide to identify patients with reduced left ventricular ejection fraction J Am Coll Cardiol 2004;43:1019-1026.[Abstract/Free Full Text]

This article has been cited by other articles:

				N. Y.-K. Chan, N. Seyedi, K. Takano, and R. Levi An Unsuspected Property of Natriuretic Peptides: Promotion of Calcium-Dependent Catecholamine Release Via Protein Kinase G-Mediated Phosphodiesterase Type 3 Inhibition Circulation, January 17, 2012; 125(2): 298 - 307. [Abstract] [Full Text] [PDF]

				T. Nishikimi, M. Ikeda, Y. Takeda, T. Ishimitsu, I. Shibasaki, H. Fukuda, H. Kinoshita, Y. Nakagawa, K. Kuwahara, and K. Nakao The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure Heart, January 15, 2012; 98(2): 152 - 161. [Abstract] [Full Text] [PDF]

				L. B. Daniels, P. Clopton, M. Potocki, C. Mueller, J. McCord, M. Richards, O. Hartmann, I. S. Anand, A. H. B. Wu, R. Nowak, et al. Influence of age, race, sex, and body mass index on interpretation of midregional pro atrial natriuretic peptide for the diagnosis of acute heart failure: results from the BACH multinational study Eur J Heart Fail, January 1, 2012; 14(1): 22 - 31. [Abstract] [Full Text] [PDF]

				J. P. Goetze B-Type Natriuretic Peptide: From Posttranslational Processing to Clinical Measurement Clin. Chem., January 1, 2012; 58(1): 83 - 91. [Abstract] [Full Text] [PDF]

				K. van den Hurk, Y. D. Reijmer, E. van den Berg, M. Alssema, G. Nijpels, P. J. Kostense, C. D. A. Stehouwer, W. J. Paulus, O. Kamp, J. M. Dekker, et al. Heart failure and cognitive function in the general population: the Hoorn Study Eur J Heart Fail, December 1, 2011; 13(12): 1362 - 1369. [Abstract] [Full Text] [PDF]

				Y. Doi, T. Ninomiya, J. Hata, Y. Hirakawa, N. Mukai, F. Ikeda, M. Fukuhara, M. Iwase, and Y. Kiyohara N-Terminal Pro-Brain Natriuretic Peptide and Risk of Cardiovascular Events in a Japanese Community: The Hisayama Study Arterioscler Thromb Vasc Biol, December 1, 2011; 31(12): 2997 - 3003. [Abstract] [Full Text] [PDF]

				K. Rychli, B. Richter, P. J. Hohensinner, K. Mahdy Ali, S. Neuhold, G. Zorn, R. Berger, D. Mortl, K. Huber, R. Pacher, et al. Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure Heart, July 15, 2011; 97(14): 1158 - 1163. [Abstract] [Full Text] [PDF]

				C. T. RUFF, D. A. MORROW, P. JAROLIM, F. REN, C. F. CONTANT, A. KAUR, S. P. CURTIS, L. LAINE, C. P. CANNON, and K. BRUNE Evaluation of NT-proBNP and High Sensitivity C-Reactive Protein for Predicting Cardiovascular Risk in Patients with Arthritis Taking Longterm Nonsteroidal Antiinflammatory Drugs J Rheumatol, June 1, 2011; 38(6): 1071 - 1078. [Abstract] [Full Text] [PDF]

				K. Damman, M. J. Ng Kam Chuen, R. J. MacFadyen, G. Y. H. Lip, D. Gaze, P. O. Collinson, H. L. Hillege, W. van Oeveren, A. A. Voors, and D. J. van Veldhuisen Volume Status and Diuretic Therapy in Systolic Heart Failure and the Detection of Early Abnormalities in Renal and Tubular Function J. Am. Coll. Cardiol., May 31, 2011; 57(22): 2233 - 2241. [Abstract] [Full Text] [PDF]

				P. Hofer, B. Syeda, J. Bergler-Klein, F. Friedrich, O. M. Lesch, B. Vyssoki, T. Binder, and H. Walter Amino-Terminal Pro-B-Type Brain Natriuretic Peptide: Screening for Cardiovascular Disease in the Setting of Alcoholism Alcohol Alcohol., May 1, 2011; 46(3): 247 - 252. [Abstract] [Full Text] [PDF]

				S. Wei, N. I. Loyo-Berrios, M. C. P. Haigney, H. Cheng, E. E. Pinnow, K. R. Mitchell, J. H. Beachy, A. M. Woodward, Y. Wang, J. P. Curtis, et al. Elevated B-Type Natriuretic Peptide Is Associated With Increased In-Hospital Mortality or Cardiac Arrest in Patients Undergoing Implantable Cardioverter-Defibrillator Implantation Circ Cardiovasc Qual Outcomes, May 1, 2011; 4(3): 346 - 354. [Abstract] [Full Text] [PDF]

				A. A. Fox and S. C. Body Assessment of Preoperative B-Type Natriuretic Peptide in Adult Surgeries: Is It Useful? Anesth. Analg., May 1, 2011; 112(5): 1005 - 1007. [Full Text] [PDF]

				A. S. Maisel, N. Katz, H. L. Hillege, A. Shaw, P. Zanco, R. Bellomo, I. Anand, S. D. Anker, N. Aspromonte, S. M. Bagshaw, et al. Biomarkers in kidney and heart disease Nephrol. Dial. Transplant., January 1, 2011; 26(1): 62 - 74. [Abstract] [Full Text] [PDF]

				S. Ozsu, A. Gulsoy, S. C. Karahan, A. Mentese, I. Nuhoglu, and T. Ozlu Diagnostic value of pleural effusion ischaemia-modified albumin in patients with cardiac failure Ann Clin Biochem, January 1, 2011; 48(1): 45 - 50. [Abstract] [Full Text] [PDF]

				G. Y. H. Lip, H.-F. Tse, and A. J. Stewart Coats Acute heart failure ODR Cardiology, January 1, 2011; 1(1): med-9780199568093-div1-00 - med-9780199568093-div1-00. [Full Text]

				R. W. Troughton, C. M. Frampton, and M. G. Nicholls Biomarker-Guided Treatment of Heart Failure: Still Waiting for a Definitive Answer J. Am. Coll. Cardiol., December 14, 2010; 56(25): 2101 - 2104. [Full Text] [PDF]

				K. Shah, P. R. Taub, and A. Maisel Chapter 35 Biomarkers in acute heart failure The ESC Textbook of Acute and Intensive Cardiac Care, December 1, 2010; 1(1): med-9780199584314-chapter - med-9780199584314-chapter. [Abstract] [Full Text] [PDF]

				E. D. Bartels, J. M. Nielsen, L. S. Bisgaard, J. P. Goetze, and L. B. Nielsen Decreased Expression of Natriuretic Peptides Associated with Lipid Accumulation in Cardiac Ventricle of Obese Mice Endocrinology, November 1, 2010; 151(11): 5218 - 5225. [Abstract] [Full Text] [PDF]

				S. Chen, S. Sen, D. Young, W. Wang, C. S. Moravec, and Q. Wu Protease corin expression and activity in failing hearts Am J Physiol Heart Circ Physiol, November 1, 2010; 299(5): H1687 - H1692. [Abstract] [Full Text] [PDF]

				K. van den Hurk, M. Alssema, O. Kamp, R. M. Henry, C. D. Stehouwer, M. Diamant, F. Boomsma, R. J. Heine, G. Nijpels, W. J. Paulus, et al. Slightly elevated B-type natriuretic peptide levels in a non-heart failure range indicate a worse left ventricular diastolic function in individuals with, as compared with individuals without, type 2 diabetes: the Hoorn Study Eur J Heart Fail, September 1, 2010; 12(9): 958 - 965. [Abstract] [Full Text] [PDF]

				J. Jiang, N. Pristera, W. Wang, X. Zhang, and Q. Wu Effect of Sialylated O-Glycans in Pro-Brain Natriuretic Peptide Stability Clin. Chem., June 1, 2010; 56(6): 959 - 966. [Abstract] [Full Text] [PDF]

				C. D. Steadman, S. Ray, L. L. Ng, and G. P. McCann Natriuretic Peptides in Common Valvular Heart Disease J. Am. Coll. Cardiol., May 11, 2010; 55(19): 2034 - 2048. [Abstract] [Full Text] [PDF]

				S. Masson, R. Latini, E. Carbonieri, L. Moretti, M. G. Rossi, S. Ciricugno, V. Milani, R. Marchioli, J. Struck, A. Bergmann, et al. The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the GISSI-heart failure (GISSI-HF) trial Eur J Heart Fail, April 1, 2010; 12(4): 338 - 347. [Abstract] [Full Text] [PDF]

				R. H. Christenson, H. M.E. Azzazy, S.-H. Duh, S. Maynard, S. L. Seliger, and C. R. deFilippi Impact of Increased Body Mass Index on Accuracy of B-Type Natriuretic Peptide (BNP) and N-Terminal proBNP for Diagnosis of Decompensated Heart Failure and Prediction of All-Cause Mortality Clin. Chem., April 1, 2010; 56(4): 633 - 641. [Abstract] [Full Text] [PDF]

				A. Noman, J. George, and A. Struthers A new use for B-type natriuretic peptide: to detect myocardial ischaemia in non-heart failure patients The British Journal of Diabetes & Vascular Disease, March 1, 2010; 10(2): 78 - 82. [Abstract] [PDF]

				N. Dong, S. Chen, J. Yang, L. He, P. Liu, D. Zheng, L. Li, Y. Zhou, C. Ruan, E. Plow, et al. Plasma Soluble Corin in Patients With Heart Failure Circ Heart Fail, March 1, 2010; 3(2): 207 - 211. [Abstract] [Full Text] [PDF]

				C. L. Wiley, S. P. Switzer, R. L. Berg, I. Glurich, and R. A. Dart Association of B-Type Natriuretic Peptide Levels With Estimated Glomerular Filtration Rate and Congestive Heart Failure Clin. Med. Res., March 1, 2010; 8(1): 7 - 12. [Abstract] [Full Text] [PDF]

				F. Sam and K. Walsh What can adiponectin say about left ventricular function? Heart, March 1, 2010; 96(5): 331 - 332. [Full Text] [PDF]

				T. Nishikimi, N. Minamino, M. Ikeda, Y. Takeda, K. Tadokoro, I. Shibasaki, H. Fukuda, Y. Horiuchi, S. Oikawa, T. Ieiri, et al. Diversity of molecular forms of plasma brain natriuretic peptide in heart failure--different proBNP-108 to BNP-32 ratios in atrial and ventricular overload Heart, March 1, 2010; 96(6): 432 - 439. [Abstract] [Full Text] [PDF]

				M. G. Daly, C. M. Frampton, and R. W. Troughton Improving Risk Stratification for Heart Failure: A Role for Serial Testing of B-Type Natriuretic Peptides? J. Am. Coll. Cardiol., February 2, 2010; 55(5): 451 - 453. [Full Text] [PDF]

				P. A. Gould, L.J. Gula, V. Bhayana, R.N. Subbiah, C. Bentley, R. Yee, G. J. Klein, A. D. Krahn, and A. C. Skanes Characterization of Cardiac Brain Natriuretic Peptide Release in Patients With Paroxysmal Atrial Fibrillation Undergoing Left Atrial Ablation Circ Arrhythm Electrophysiol, February 1, 2010; 3(1): 18 - 23. [Abstract] [Full Text] [PDF]

				W.-C. Chen, K. D. Tran, and A. S. Maisel Biomarkers in heart failure Heart, February 1, 2010; 96(4): 314 - 320. [Full Text] [PDF]

				S. C. Mathai, M. Bueso, L. K. Hummers, D. Boyce, N. Lechtzin, J. Le Pavec, A. Campo, H. C. Champion, T. Housten, P. R. Forfia, et al. Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension Eur. Respir. J., January 1, 2010; 35(1): 95 - 104. [Abstract] [Full Text] [PDF]

				G. C.M. Linssen, S. J.L. Bakker, A. A. Voors, R. T. Gansevoort, H. L. Hillege, P. E. de Jong, D. J. van Veldhuisen, R. O.B. Gans, and D. de Zeeuw N-terminal pro-B-type natriuretic peptide is an independent predictor of cardiovascular morbidity and mortality in the general population Eur. Heart J., January 1, 2010; 31(1): 120 - 127. [Abstract] [Full Text] [PDF]

				Y. Liu, D. Abendschein, G. E. Woodard, R. Rossin, K. McCommis, J. Zheng, M. J. Welch, and P. K. Woodard Molecular Imaging of Atherosclerotic Plaque with 64Cu-Labeled Natriuretic Peptide and PET J. Nucl. Med., January 1, 2010; 51(1): 85 - 91. [Abstract] [Full Text] [PDF]

				E. Di Angelantonio, R. Chowdhury, N. Sarwar, K. K. Ray, R. Gobin, D. Saleheen, A. Thompson, V. Gudnason, N. Sattar, and J. Danesh B-Type Natriuretic Peptides and Cardiovascular Risk: Systematic Review and Meta-Analysis of 40 Prospective Studies Circulation, December 1, 2009; 120(22): 2177 - 2187. [Abstract] [Full Text] [PDF]

				L. B. Daniels and E. Barrett-Connor Can Natriuretic Peptides Help Identify Heart Failure Patients for Whom Statins Are Beneficial? J. Am. Coll. Cardiol., November 10, 2009; 54(20): 1860 - 1861. [Full Text] [PDF]

				R. K. Rogers, J. Stehlik, G. J. Stoddard, T. Greene, S. P. Collins, W. F. Peacock, A. D. Maisel, P. Clopton, and A. D. Michaels Adjusting for clinical covariates improves the ability of B-type natriuretic peptide to distinguish cardiac from non-cardiac dyspnoea: a sub-study of HEARD-IT Eur J Heart Fail, November 1, 2009; 11(11): 1043 - 1049. [Abstract] [Full Text] [PDF]

				E. M. Kanoupakis, E. G. Manios, and P. E. Vardas Predicting future shocks in implantable cardioverter defibrillator recipients: the role of biomarkers Europace, November 1, 2009; 11(11): 1434 - 1439. [Abstract] [Full Text] [PDF]

				J. D. Gottlieb, A. R. Schwartz, J. Marshall, P. Ouyang, L. Kern, V. Shetty, M. Trois, N. M. Punjabi, C. Brown, S. S. Najjar, et al. Hypoxia, Not the Frequency of Sleep Apnea, Induces Acute Hemodynamic Stress in Patients With Chronic Heart Failure J. Am. Coll. Cardiol., October 27, 2009; 54(18): 1706 - 1712. [Abstract] [Full Text] [PDF]

				D. Bolliger, M. D. Seeberger, and M. Filipovic Pre-Operative Cardiac Risk Assessment in Noncardiac Surgery: Are Natriuretic Peptides the Magic Bullet? J. Am. Coll. Cardiol., October 20, 2009; 54(17): 1607 - 1608. [Full Text] [PDF]

				P. A. Scott, J. Barry, P. R. Roberts, and J. M. Morgan Brain natriuretic peptide for the prediction of sudden cardiac death and ventricular arrhythmias: a meta-analysis Eur J Heart Fail, October 1, 2009; 11(10): 958 - 966. [Abstract] [Full Text] [PDF]

				J-C Lega, Y Lacasse, L Lakhal, and S Provencher Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis Thorax, October 1, 2009; 64(10): 869 - 875. [Abstract] [Full Text] [PDF]

				B Dieplinger, A Gegenhuber, M Haltmayer, and T Mueller Evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure in patients with shortness of breath Heart, September 15, 2009; 95(18): 1508 - 1513. [Abstract] [Full Text] [PDF]

				S. M. Dunlay, Y. Gerber, S. A. Weston, J. M. Killian, M. M. Redfield, and V. L. Roger Prognostic Value of Biomarkers in Heart Failure: Application of Novel Methods in the Community Circ Heart Fail, September 1, 2009; 2(5): 393 - 400. [Abstract] [Full Text] [PDF]

				G. Casals, J. Ros, A. Sionis, M. M. Davidson, M. Morales-Ruiz, and W. Jimenez Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H550 - H555. [Abstract] [Full Text] [PDF]

				S. Gao, C.-L. Long, R.-H. Wang, and H. Wang KATP activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function Cardiovasc Res, August 1, 2009; 83(3): 444 - 456. [Abstract] [Full Text] [PDF]

				G. C.M. Linssen, K. Damman, H. L. Hillege, G. Navis, D. J. van Veldhuisen, and A. A. Voors Urinary N-Terminal Prohormone Brain Natriuretic Peptide Excretion in Patients With Chronic Heart Failure Circulation, July 7, 2009; 120(1): 35 - 41. [Abstract] [Full Text] [PDF]

				R. V. Shah, A. A. Chen-Tournoux, M. H. Picard, R. R.J. van Kimmenade, and J. L. Januzzi Serum Levels of the Interleukin-1 Receptor Family Member ST2, Cardiac Structure and Function, and Long-Term Mortality in Patients With Acute Dyspnea Circ Heart Fail, July 1, 2009; 2(4): 311 - 319. [Abstract] [Full Text] [PDF]

				A. Cohen-Solal, D. Logeart, B. Huang, D. Cai, M. S. Nieminen, and A. Mebazaa Lowered B-Type Natriuretic Peptide in Response to Levosimendan or Dobutamine Treatment Is Associated With Improved Survival in Patients With Severe Acutely Decompensated Heart Failure J. Am. Coll. Cardiol., June 23, 2009; 53(25): 2343 - 2348. [Abstract] [Full Text] [PDF]

				M. Gheorghiade and P. S. Pang Are BNP Changes During Hospitalization for Heart Failure a Reliable Surrogate for Predicting the Effects of Therapies on Post-Discharge Mortality? J. Am. Coll. Cardiol., June 23, 2009; 53(25): 2349 - 2352. [Full Text] [PDF]

				S. S. Chugh and K. Reinier Predicting Sudden Death in the General Population: Another Step, N Terminal B-Type Natriuretic Factor Levels Circulation, June 9, 2009; 119(22): 2863 - 2864. [Full Text] [PDF]

				S Dhar, G S Pressman, S Subramanian, S Kaul, S Gollamudi, E J Bloom, and V M Figueredo Natriuretic peptides and heart failure in the patient with chronic kidney disease: a review of current evidence Postgrad. Med. J., June 1, 2009; 85(1004): 299 - 302. [Abstract] [Full Text] [PDF]

				C. Vassalle and M. G. Andreassi Genetic Polymorphisms of the Natriuretic Peptide System in the Pathogenesis of Cardiovascular Disease: What Lies on the Horizon? Clin. Chem., May 1, 2009; 55(5): 878 - 887. [Abstract] [Full Text] [PDF]

				D. Bolliger, M. D. Seeberger, G. A. L. Lurati Buse, P. Christen, B. Rupinski, L. Gurke, and M. Filipovic A Preliminary Report on the Prognostic Significance of Preoperative Brain Natriuretic Peptide and Postoperative Cardiac Troponin in Patients Undergoing Major Vascular Surgery Anesth. Analg., April 1, 2009; 108(4): 1069 - 1075. [Abstract] [Full Text] [PDF]

				A. Bernus, B. D. Wagner, F. Accurso, A. Doran, H. Kaess, and D. D. Ivy Brain Natriuretic Peptide Levels in Managing Pediatric Patients With Pulmonary Arterial Hypertension Chest, March 1, 2009; 135(3): 745 - 751. [Abstract] [Full Text] [PDF]

				A. G. Semenov, A. B. Postnikov, N. N. Tamm, K. R. Seferian, N. S. Karpova, M. N. Bloshchitsyna, E. V. Koshkina, M. I. Krasnoselsky, D. V. Serebryanaya, and A. G. Katrukha Processing of Pro-Brain Natriuretic Peptide Is Suppressed by O-Glycosylation in the Region Close to the Cleavage Site Clin. Chem., March 1, 2009; 55(3): 489 - 498. [Abstract] [Full Text] [PDF]

				R. W. Troughton and A. M. Richards B-type natriuretic peptides and echocardiographic measures of cardiac structure and function. J. Am. Coll. Cardiol. Img., February 1, 2009; 2(2): 216 - 225. [Abstract] [Full Text] [PDF]

				M. Kruger, S. Kotter, A. Grutzner, P. Lang, C. Andresen, M. M. Redfield, E. Butt, C. G. dos Remedios, and W. A. Linke Protein Kinase G Modulates Human Myocardial Passive Stiffness by Phosphorylation of the Titin Springs Circ. Res., January 2, 2009; 104(1): 87 - 94. [Abstract] [Full Text] [PDF]

				M. Andreassen, I. Raymond, C. Kistorp, P. Hildebrandt, J. Faber, and L. O. Kristensen IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population Eur. J. Endocrinol., January 1, 2009; 160(1): 25 - 31. [Abstract] [Full Text] [PDF]

				J. McMurray, M. Petrie, K. Swedberg, M. Komajda, S. Anker, and R. Gardner CHAPTER 23 Heart Failure ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				L. Senggunprai, K. Yoshinari, M. Shimada, and Y. Yamazoe Involvement of ST1B Subfamily of Cytosolic Sulfotransferase in Kynurenine Metabolism to Form Natriuretic Xanthurenic Acid Sulfate J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 789 - 798. [Abstract] [Full Text] [PDF]

				G. Vila, M. Resl, D. Stelzeneder, J. Struck, C. Maier, M. Riedl, M. Hulsmann, R. Pacher, A. Luger, and M. Clodi Plasma NT-proBNP increases in response to LPS administration in healthy men J Appl Physiol, December 1, 2008; 105(6): 1741 - 1745. [Abstract] [Full Text] [PDF]

				R. Tagore, L. H. Ling, H. Yang, H.-Y. Daw, Y.-H. Chan, and S. K. Sethi Natriuretic Peptides in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2008; 3(6): 1644 - 1651. [Abstract] [Full Text] [PDF]

				G. Lippi, G. Targher, and S. Z. Goldhaber Natriuretic Peptides for Assessing the Prognosis of Acute Pulmonary Embolism Chest, June 1, 2008; 133(6): 1531 - 1532. [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) All Versions of this Article: j.jacc.2007.09.021v1 50/25/2357    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (116) Citing Articles via Google Scholar Google Scholar Articles by Daniels, L. B. Articles by Maisel, A. S. Search for Related Content PubMed PubMed Citation Articles by Daniels, L. B. Articles by Maisel, A. S.