Perioperative B-type Natriuretic Peptide/N-terminal pro-B-type Natriuretic Peptide: Next Steps to Clinical Practice.

Anesthesiology, V 123 • No 2 246 August 2015 T HE heart is not only a pumping organ but also an endocrine organ. B-type natriuretic peptide (BNP) is secreted primarily by cardiac ventricular myocytes in response to increased ventricular wall stress induced by volume expansion, pressure overload, or ischemia.1 BNP protein formation begins with intracellular translation into a large preprohormone that is processed to pro-brain natriuretic peptide (proBNP) and then is cleaved and released into the circulation as active BNP and biologically inactive N-terminal proBNP (NT-proBNP) fragment.1 Commercial assays are available to measure circulating BNP and NT-proBNP. Although BNP has known compensatory natriuretic, diuretic, and vasodilatory properties, studies of both ambulatory and surgical patients have found that elevations of circulating BNP or NT-proBNP significantly associate with increased adverse cardiac events.1–3 Worldwide, approximately 200 million noncardiac surgeries are performed every year, with 30-day postoperative mortality estimated at approximately 2%.4,5 A number of studies therefore have evaluated whether elevations in preoperative BNP or NT-proBNP predict cardiac morbidity and mortality after noncardiac surgeries. In this issue of ANEsTHEsIology, Potgieter et al.6 provide an elegant comparison of two different approaches to meta-analysis of 14 studies of noncardiac surgical patients (n = 2,196) that assess the association between elevated preoperative NT-proBNP and the composite outcome of 30-day postoperative mortality or nonfatal myocardial infarction (MI). The authors report that meta-analysis that aggregates study findings using the different optimal cut-points and corresponding odd ratios (oRs) established for each individual study cohort (i.e., aggregate data approach) results in a substantially inflated reported oR for association between NT-proBNP and 30-day postoperative outcome when compared with meta-analysis that combines individual-level data across all studies to define one optimal NT-proBNP cut-point to be used across all study cohorts (i.e., individual patient-level data approach). These findings provide an important warning regarding likely overestimation of effect size reported in aggregate data metaanalyses of biomarker studies. However, although the results of the individual patient-level data meta-analysis by Potgieter et al. demonstrate a marked shrinkage in resulting oR from the oR identified using aggregate data meta-analysis, their findings still highlight a clinically relevant effect size (oR for association between NT-proBNP >367.15 pg/ml and 30-day outcome = 3.61; 95% CI, 2.73 to 4.78). Thus, the question remains regarding what next studies and steps can be undertaken to determine whether perioperative NT-proBNP or BNP assessments can be used in clinical practice to predict and mitigate postoperative morbidity and mortality. A key impediment to moving evaluation of perioperative BNP or NT-proBNP into routine clinical practice for risk stratification and management of surgical patients is the lack of clarity from presently available literature regarding what cut-points of these biomarkers should be used to determine the risk. several factors contribute to this lack of clarity. First, although both elevated BNP and NT-proBNP associate with adverse cardiovascular outcomes in ambulatory and surgical cohorts,1–3 NT-proBNP has a longer half-life than BNP and typically has twoto three-fold higher circulating concentrations than BNP. For clinical use, any cut-points identified in the literature should be considered specific to the BNP or NT-proBNP assay that was used. second, BNP and Perioperative B-type Natriuretic Peptide/N-terminal pro-B-type Natriuretic Peptide