B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease

Abstract

Background: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use.

Methods: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression.

Results: Five hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45-3.19; p = 0.0001) and 1.27 for composite events (1.04-1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease.

Conclusions: Conventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management.

Trial registration: Clinicaltrials.gov, NCT00403351 Registered on 22 November 2006.

Keywords: B-type natriuretic peptide; Coronary angiography; Coronary artery disease; Mortality; Risk.

Conflict of interest statement

Ethics approval and consent to participate

The ARM-CAD Study was approved by Ethics Committees from Monash University, Melbourne, Australia (2006/831MC) and The Alfred Melbourne, Australia (38/07).

All patients provided written informed consent.

Consent for publication

Not applicable – all original data.

Competing interests

MDF reports grants from Novartis and personal fees from AstraZeneca, Novartis and Pfizer, all outside the submitted work. DA has received speakers’ honoraria from Roche Diagnostics and Siemens Diagnostics, outside the submitted work. PC reports personal speaking honoraria from Menarini, AstraZenica, Bayer, Itamar Medical, Abbott and Ferring Pharmaceuticals, all outside the submitted work. The other authors declare that they have no competing interests.

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Figures

Fig. 1

Flowchart for the ARM-CAD study. Includes independently adjudicated events subdivided by baseline BNP level. BNP, B-type natriuretic peptide; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting (PCI and CABG are not mutually exclusive)

Fig. 2

Kaplan Meier curves for death, myocardial infarction or stroke. Apart from coronary angiogram results, clinicians remained blinded to all other baseline risk markers. p values are a chi-squared log-rank test for trend performed at a landmark censoring of 1 year and at the median 5-year follow-up. Corresponding p values for all-cause mortality alone at 5-year follow-up are a BNP p = 0.001, b hs-CRP p = 0.27, c central augmentation pressure p = 0.38, d low/high-frequency HRV p = 0.30, e Framingham risk p = 0.026, f Angiographic coronary disease p = 0.09. *Post hoc exclusion of patients with atrial arrhythmias at baseline or follow-up had no impact on results. †Post hoc exclusion of patients with any revascularization resulted in ptrend = 0.029 for death, MI or CVA at 5-year follow-up, and 0.18 for mortality alone. CAD, coronary artery disease

Fig. 3

Kaplan-Meier adverse event curves according to the pre-specified BNP cut-point of 100 pg/mL for a: all-cause mortality; and b: death, MI or stroke. BNP, B-type natriuretic peptide; MI, myocardial infarction

Fig. 4

Risk contour map for adjusted predicted mortality according to age and BNP. Example: 75-year-old patient with a BNP of 25 pg/mL has a predicted 5-year mortality of 0–5%, compared to 10–20% in a patient of the same age with a BNP of 200 pg/mL. Note that risk estimates are based on the ARM-CAD cohort of patients with extensive modification of risk factors and concomitant disease, revascularization as required, and highly involved secondary care physicians