Plasma concentration of brain natriuretic peptide as a biochemical marker for the evaluation of right ventricular overload and mortality in chronic respiratory disease

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Abstract

The purpose of this study was to evaluate whether the plasma brain natriuretic peptide (BNP) concentration is a useful marker of right ventricular (RV) overload and whether it has prognostic value as a predictor of death in patients with chronic respiratory disease (CRD). We measured the plasma BNP and atrial natriuretic peptide (ANP) concentrations in 31 consecutive patients with CRD who underwent right-heart catheterization to evaluate pulmonary hypertension. All patients were followed for >12 months. The plasma BNP concentration closely correlated with the mean pulmonary artery pressure and pulmonary vascular resistance (r=0.62, P<0.0005 and r=0.85, P<0.0001), and showed a weak linear correlation with cardiac output (r=−0.36, P<0.05). During the follow-up period, 5 (16%) end-stage CRD deaths (4 RV heart failure and 1 respiratory infection) and 2 non-end-stage CRD deaths occurred. In a stepwise multivariate Cox proportional-hazards regression analysis including age, sex, BNP, ANP, hemodynamic variables and the ratio of PaO2 to fraction of inspired oxygen, only BNP (P<0.05) was an independent predictor of end-stage CRD death. The upward and leftward shift in the receiver operating characteristic curve between patients with end-stage CRD death and those without was greater for BNP than for ANP. Our findings suggest that the plasma BNP concentration may be an inexpensive, simple and useful marker of RV overload and end-stage CRD death in CRD patients. These preliminary results need to be confirmed in a large series of CRD patients.

Introduction

Human brain natriuretic peptide (BNP) is a 32-amino acid peptide which is similar to atrial natriuretic peptide (ANP) in structure and shares the same guanylate cyclase receptors on endothelial cells [1], [2]. Like ANP, BNP possesses potent diuretic and natriuretic activity, vasorelaxant activity for both the pulmonary and systemic circulation, and an inhibitory effect on renin and aldosterone secretion [3], [4]. Unlike ANP, BNP is mainly synthesized in and secreted from the ventricular myocardium [5]. Recently, plasma BNP has been postulated to be a simple and useful marker for the assessment of the severity of disease and mortality in patients with left ventricular (LV) overload [5], [6], [7], [8], [9], [10]. However, the clinical significance of the plasma BNP concentration in patients with isolated right ventricular (RV) overload has been less extensively studied than in patients with LV overload.

Several studies have shown that the plasma BNP concentration increases with the degree of hypoxia in patients with chronic respiratory disease (CRD) [11], [12]. A recent study reported in 19 CRD patients that plasma BNP weakly correlated with systolic pulmonary artery pressure (PAP) estimated by Doppler echocardiogrphy (r=0.43, P=0.068) [13]. However, this has not been confirmed by invasive methods in CRD patients.

Recently, Omland and coworkers showed that the plasma BNP but not ANP provided additional prognostic information beyond the LV ejection fraction after an acute myocardial infarction [8]. Also, Tsutamoto and coworkers reported that the plasma BNP is a stronger prognostic predictor than either the ANP or LV ejection fraction in patients with congestive heart failure [9]. Therefore, the plasma BNP may be an important prognostic indicator in patients with LV overload. However, this has not been investigated in patients with isolated RV overload.

In the present study, we measured the plasma BNP and ANP concentrations in 31 consecutive patients with CRD who underwent a right-heart catheterization for the evaluation of pulmonary hypertension (PH). All the patients were followed for >12 months. Our objective was to examine whether the plasma BNP is a useful marker for the evaluation of RV overload and end-stage CRD death in CRD patients.

Section snippets

Subjects

The study population consisted of 31 consecutive patients with CRD who underwent right-heart catheterization for the evaluation of PH (Table 1). The median duration of CRD was 16 years (interquartile range 11–20). The cause of CRD was the result of old pulmonary tuberculosis in 15 patients, chronic obstructive pulmonary disease (COPD) in 12 patients, and pulmonary fibrosis in four patients. None of the patients had a medical history of ischemic heart disease, valvular heart disease, systemic

Results

The patients were divided into two groups according to their PAP. The PH group consisted of 15 patients with a mean PAP >20 mm Hg. The non-PH group consisted of 16 patients with a mean PAP≤20 mm Hg. The plasma concentrations of BNP and ANP and the ratio of BNP to ANP in the PH group were significantly higher than those in the non-PH group (Table 1). The mean PAP, PVR, RVEDP and mean RAP were significantly higher in the PH group than in the non-PH group. The PaO2/FIO2 was significantly lower in

Discussion

The present study demonstrated that the BNP concentration correlated with PVR, PAP and CO in CRD patients, and independently associated with end-stage CRD death. Our findings suggest that the measurements of plasma BNP concentration may be useful for the evaluation of RV overload and end-stage CRD death in CRD patients. This study consisted of a small population of CRD patients. Thus, additional prospective studies should be carried out in a larger CRD population to confirm these results.

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Acknowledgements

We thank Kouichi Iwasaki, MD, Atsushi Oyama, MD, Yoko Hanaoka, MD, Motoyasu Okuno, MD, Hiroshi Saito, MD, Tatsuo Ogimi, MD and Hiroshi Ariyoshi, MD at Aichi prefecture hospital for help with collecting the blood samples and the critical reading of the manuscript. We also thank Shionogi Co., Ltd. for gifts of BNP and ANP reagents.

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