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CLINICAL RESEARCH: BIOMARKERS AND CARDIAC SURGERY

Is a Pre-Operative Brain Natriuretic Peptide or N-Terminal Pro–B-Type Natriuretic Peptide Measurement an Independent Predictor of Adverse Cardiovascular Outcomes Within 30 Days of Noncardiac Surgery?

A Systematic Review and Meta-Analysis of Observational Studies

Ganesan Karthikeyan, MD, DM^_*,,,||, Ross A. Moncur, BSc^¶, Oren Levine, BSc^#, Diane Heels-Ansdell, MSc, Matthew T.V. Chan, MD, MSc^_**, Pablo Alonso-Coello, MD, MSc^,, Salim Yusuf, MBBS, DPhil^_*,,,||, Daniel Sessler, MD, Juan Carlos Villar, MD, PhD^||||, Otavio Berwanger, MD, PhD^¶¶, Matthew McQueen, MB, ChB, PhD^,,||, Anna Mathew, MD^##, Stephen Hill, PhD, Simon Gibson, MD^_***, Colin Berry, MD, Huei-Ming Yeh, MD and P.J. Devereaux, MD, PhD^,,||,_*

^_* Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
Department of Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
Department of Clinical Epidemiology and Biostatistics, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
Department of Pathology and Molecular Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
^|| Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
^¶ Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
^# School of Medicine, Queen's University, Kingston, Ontario, Canada
^_** Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, China
Iberoamerican Cochrane Center, Hospital Sant Pau, Barcelona, Spain
CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Department of Outcomes Research, The Cleveland Clinic, Cleveland, Ohio
^|||| Facultad de Medicina, Universidad de la Sabana, Bogotá, Colombia
^¶¶ Research Institute (IEP-HCor), Hospital do Coração-/HCor, Sao Paulo, Brazil
^## Department of Medicine, University of Western Ontario in London, London, Ontario, Canada
^_*** Department of General and Vascular Surgery, Gartnavel General Hospital, Glasgow, United Kingdom
BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom
Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan

Manuscript received January 22, 2009; revised manuscript received May 11, 2009, accepted June 1, 2009.

^_* Reprint requests and correspondence: Dr. P. J. Devereaux, McMaster University Health Sciences Centre, Room 2C8, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z5 (Email: philipj{at}mcmaster.ca).

Objectives: We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro–B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery.

Background: Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting.

Methods: We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model.

Results: Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I² = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I² = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I² = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I² = 62.2%); the p value for interaction was 0.28.

Conclusions: These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.

Key Words: perioperative myocardial infarction • brain natriuretic peptide • perioperative risk

Abbreviations and Acronyms   BNP = brain natriuretic peptide   LVEF = left ventricular ejection fraction   MI = myocardial infarction   NT-proBNP = N-terminal pro–B-type natriuretic peptide   OR = odds ratio

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