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Observational Study
. 2018 Jul;154(1):126-135.
doi: 10.1016/j.chest.2018.01.009. Epub 2018 Jan 31.

Baseline and Serial Brain Natriuretic Peptide Level Predicts 5-Year Overall Survival in Patients With Pulmonary Arterial Hypertension: Data From the REVEAL Registry

Robert P Frantz  1 , Harrison W Farber  2 , David B Badesch  3 , C Greg Elliott  4 , Adaani E Frost  5 , Michael D McGoon  6 , Carol Zhao  7 , David R Mink  8 , Mona Selej  7 , Raymond L Benza  9
Affiliations
Observational Study

Baseline and Serial Brain Natriuretic Peptide Level Predicts 5-Year Overall Survival in Patients With Pulmonary Arterial Hypertension: Data From the REVEAL Registry

Robert P Frantz et al. Chest. 2018 Jul.

Abstract

Background: Plasma brain natriuretic peptide (BNP) level is a prognostic biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term overall survival (OS) was investigated in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year observational, multicenter, US registry of patients with PAH.

Methods: Patients were ≥ 18 years of age, met right heart catheterization criteria at rest, had World Health Organization group I PAH, and had BNP measurement at enrollment. Optimal BNP threshold was obtained via receiver operating characteristic curve analysis. OS was compared in patients with low (≤ 340 pg/mL) vs high (> 340 pg/mL) BNP at baseline; changes between baseline and last assessment were also examined. Patients were categorized based on baseline (low or high) and follow-up (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared using Cox regression.

Results: Overall, 1,426 patients were analyzed. Mortality risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6; 95% CI, 3.0-4.2). BNP change analysis at ≤ 1 year postenrollment demonstrated that the low-low group had the lowest and the high-high group had the highest 5-year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also correlated with change of risk of death.

Conclusions: Baseline BNP threshold of 340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP reduction at 1 year since enrollment was associated with decreased mortality risk, whereas an increase in BNP at 1 year was associated with an increased mortality risk, supporting BNP as a surrogate marker of PAH survival.

Keywords: biomarkers; brain natriuretic peptide; mortality; pulmonary arterial hypertension; survival.

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Figures

Figure 1
Figure 1
Kaplan-Meier estimates of 5-y overall survival for patients with World Health Organization group 1 peripheral arterial hypertension stratified by baseline BNP value. BNP = brain natriuretic peptide; HR = hazard ratio; mOS = median survival time.
Figure 2
Figure 2
A, B, Kaplan-Meier estimates of 5-y overall survival according to change in BNP value relative to baseline (N = 1,426). A, Change in BNP from baseline to last assessment within 1 y postenrollment. Patients who did not have any BNP assessment within 1 y postbaseline were classified as no change in BNP. B, Change in BNP from baseline to last assessment within 5 y of enrollment. Patients who did not have any BNP assessment postbaseline were classified as no change in BNP. See Figure 1 legend for expansion of abbreviations.
Figure 2
Figure 2
A, B, Kaplan-Meier estimates of 5-y overall survival according to change in BNP value relative to baseline (N = 1,426). A, Change in BNP from baseline to last assessment within 1 y postenrollment. Patients who did not have any BNP assessment within 1 y postbaseline were classified as no change in BNP. B, Change in BNP from baseline to last assessment within 5 y of enrollment. Patients who did not have any BNP assessment postbaseline were classified as no change in BNP. See Figure 1 legend for expansion of abbreviations.
Figure 3
Figure 3
Kaplan-Meier estimates of 5-y overall survival, by BNP score at baseline. NA = not applicable. See Figure 1 legend for expansion of other abbreviations.
See this image and copyright information in PMC

Comment in

  • Response.
    Frantz RP, Zhao C, Farber HW, Badesch DB, Elliott CG, Frost AE, McGoon MD, Mink DR, Selej M, Benza RL. Frantz RP, et al. Chest. 2018 Nov;154(5):1262-1264. doi: 10.1016/j.chest.2018.07.033. Chest. 2018. PMID: 30409362 No abstract available.
  • Untangling BNP and BMI: Does Obesity Limit the Predictive Capability of BNP in PAH?
    Medrek SK, Melendres-Groves L. Medrek SK, et al. Chest. 2018 Nov;154(5):1262. doi: 10.1016/j.chest.2018.04.049. Chest. 2018. PMID: 30409363 No abstract available.

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