Associates of an Elevated Natriuretic Peptide Level in Stable Heart Failure Patients: Implications for Targeted Management

Background. Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. Methods. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e′) was measured. Results. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e′, creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e′ and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Conclusion. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

[1]  C. Watson,et al.  Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. , 2013, JAMA.

[2]  R. Akdemir,et al.  Changes in Serum Natriuretic Peptide Levels after Percutaneous Closure of Small to Moderate Ventricular Septal Defects , 2012, TheScientificWorldJournal.

[3]  M. Böhm,et al.  Biomarkers: optimizing treatment guidance in heart failure , 2011, Clinical Research in Cardiology.

[4]  D. Moertl,et al.  N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure a 3-arm, prospective, randomized pilot study. , 2010, Journal of the American College of Cardiology.

[5]  C. Frampton,et al.  N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) trial. , 2009, Journal of the American College of Cardiology.

[6]  D. Phelan,et al.  Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. , 2009, Journal of the American College of Cardiology.

[7]  E. Okello,et al.  Treatment with spironolactone for 24 weeks decreases the level of matrix metalloproteinases and improves cardiac function in patients with chronic heart failure of ischemic etiology. , 2009, The Canadian journal of cardiology.

[8]  H. Nakahama,et al.  Impact of left ventricular end-diastolic wall stress on plasma B-type natriuretic peptide in heart failure with chronic kidney disease and end-stage renal disease. , 2009, Clinical chemistry.

[9]  A. Cohen-Solal,et al.  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. , 2009, Journal of the American College of Cardiology.

[10]  D. Moertl,et al.  B-type natriuretic peptide predicts benefit from a home-based nurse care in chronic heart failure. , 2009, Journal of cardiac failure.

[11]  G. Filippatos,et al.  Determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation and preserved left ventricular ejection fraction , 2009, Clinical Research in Cardiology.

[12]  Peter Buser,et al.  BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. , 2009, JAMA.

[13]  Gianni Tognoni,et al.  Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial). , 2008, Journal of the American College of Cardiology.

[14]  J. Svendsen,et al.  ANP and BNP in atrial fibrillation before and after cardioversion--and their relationship to cardiac volume and function. , 2008, International journal of cardiology.

[15]  T. Inomata,et al.  Prognostic utility of B-type natriuretic peptide assessment in stable low-risk outpatients with nonischemic cardiomyopathy after decompensated heart failure. , 2008, Journal of the American College of Cardiology.

[16]  C. Phillips,et al.  Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure. , 2007, Journal of the American College of Cardiology.

[17]  A. Cohen-Solal,et al.  Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. , 2007, Journal of the American College of Cardiology.

[18]  R. Rodeheffer,et al.  Alternate circulating pro-B-type natriuretic peptide and B-type natriuretic peptide forms in the general population. , 2007, Journal of the American College of Cardiology.

[19]  Kenneth McDonald,et al.  Diastolic Heart Failure: Evidence of Increased Myocardial Collagen Turnover Linked to Diastolic Dysfunction , 2007, Circulation.

[20]  Y. Kihara,et al.  B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure. , 2006, Journal of the American College of Cardiology.

[21]  Richard B Devereux,et al.  Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardio , 2005, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[22]  H Robert Bergen,et al.  Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Dobson,et al.  How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review , 2005, BMJ : British Medical Journal.

[24]  J. Bartunek,et al.  Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy. , 2004, Journal of the American College of Cardiology.

[25]  Satoko Nakamura,et al.  Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[26]  N. Lamblin,et al.  B-type natriuretic peptide and peak exercise oxygen consumption provide independent information for risk stratification in patients with stable congestive heart failure. , 2004, Journal of the American College of Cardiology.

[27]  Gabriel Thabut,et al.  Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure. , 2004, Journal of the American College of Cardiology.

[28]  J. Knowles,et al.  Ventricular expression of natriuretic peptides in Npr1(-/-) mice with cardiac hypertrophy and fibrosis. , 2002, American journal of physiology. Heart and circulatory physiology.

[29]  M. Vogeser,et al.  Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure. , 2001, Journal of the American College of Cardiology.

[30]  F. Alla,et al.  Limitation of Excessive Extracellular Matrix Turnover May Contribute to Survival Benefit of Spironolactone Therapy in Patients With Congestive Heart Failure: Insights From the Randomized Aldactone Evaluation Study (RALES) , 2000, Circulation.

[31]  Kenji Nakamura,et al.  Cardiac fibrosis in mice lacking brain natriuretic peptide. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[32]  C. Frampton,et al.  Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations , 2000, The Lancet.

[33]  A. Struthers,et al.  Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. , 1997, Cardiovascular research.

[34]  L. Stevenson,et al.  The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. , 1989, JAMA.

[35]  N. Reichek,et al.  Noninvasive Determination of Left Ventricular End‐systolic Stress: Validation of the Method and Initial Application , 1982, Circulation.

[36]  J. Ferrières,et al.  Usefulness of Inhospital Change in B‐Type Natriuretic Peptide Levels in Predicting Long‐Term Outcome in Elderly Patients Admitted for Decompensated Heart Failure , 2007 .