Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT)

Abstract

Background-Neurohormones are considered markers of heart failure progression. We examined whether changes in brain natriuretic peptide (BNP) and norepinephrine (NE) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial. Methods and Results-Plasma BNP and NE were measured before randomization and during follow-up in Ϸ4300 patients in the Valsartan Heart Failure Trial. The relation between baseline BNP and NE and all-cause mortality and first morbid event (M&M) was analyzed in subgroups, with values above and below the median, and by quartiles. The change and percent change from baseline to 4 and 12 months in BNP and NE were also analyzed by quartiles for subsequent M&M. Risk ratios for M&M were calculated using a Cox proportional hazard model. Risk ratio of M&M for patients with baseline BNP or NE above the median was significantly higher than that for patients with values below the median. Baseline BNP and NE in quartiles also showed a quartile-dependent increase in M&M. BNP had a stronger association with M&M than NE. Patients with the greatest percent decrease in BNP and NE from baseline to 4 and 12 months had the lowest whereas patients with greatest percent increase in BNP and NE had the highest M&M. Conclusions-Not only are plasma BNP and NE important predictors of heart failure M&M, but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials.

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

“…Because a high norepinephrine level is an established risk factor for cardiac events and mortality (17)(18)(19)(20)(21)(22), our findings suggest that elevated norepinephrine may contribute to the increased risk of cardiac events associated with depressive symptoms (7). It is well known that norepinephrine is increased in patients with heart failure, correlates with the severity of heart failure, and is associated with increased mortality in cardiac patients (28).…”

“…High catecholamine levels can damage cardiac myocytes (15,16) and have been associated with cardiac events and mortality in a variety of clinical and population-based samples (17)(18)(19)(20)(21)(22). Thus, altered autonomic tone may contribute to adverse cardiac outcomes in patients with depression.…”

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

“…ANP and BNP are well‐established markers of both acute and chronic HF, and the circulating levels of NPs have been shown to correspond to the degree of LV dysfunction 124. In addition, NPs provide long‐term prognostic value in HF patients and in those with acute cardiac ischemia 125, 126. There is also evidence that levels of circulating NP provide predictive value in the healthy population 127.…”

Clinical Significance of B-Type Natriuretic Peptide in the Assessment of Untreated Hypertension

“…[3][4][5] The plasma level of B-type natriuretic peptide (BNP) is well established as a useful marker of cardiac dysfunction, prognosis and response to treatment in patients with heart failure. [6][7][8][9] In patients with heart failure, secretion of BNP increases in proportion to the severity of left ventricular (LV) dysfunction, as indicated by the pulmonary capillary wedge pressure and LV end-diastolic pressure or the New York Heart Association class. 6,10 However, the measurement of BNP for clinical guidelines in hypertension is not recommended at present.…”