NT-proBNP May Hold the Key to Predicting Cardiac Risk Before Noncardiac Surgery

Measuring N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels preoperatively among patients scheduled to undergo inpatient noncardiac surgery can strongly predict the risk of major cardiac events and death, according to new research.

Right now, most patients who undergo cardiac risk assessment prior to noncardiac surgery are referred for noninvasive testing like stress and nuclear studies, which can be costly and time-consuming.

“We spend a lot of time and energy right now in trying to do preoperative evaluation to provide people with our ethical obligation to let them understand both the risk and benefit of surgery, and this shows that a very simple, readily available rapid blood test can give you much better risk prediction then the current strategies that we're using,” senior author P.J. Devereaux, MD, PhD (McMaster University and Population Health Research Institute, Hamilton, Canada), told TCTMD.

For the study, published online ahead of print in the Annals of Internal Medicine, Devereaux, along with Emmanuelle Duceppe, MD (McMaster University and Population Health Research Institute), and colleagues, prospectively measured NT-proBNP levels before inpatient noncardiac surgery and troponin T levels for 3 days after the procedure in 10,402 patients ages 45 or older.

On multivariate analysis, increased NT-proBNP levels above 100 pg/mL were directly associated with increased risk of the primary outcome—a composite of vascular death and myocardial injury after noncardiac surgery—as well as the composite of all-cause mortality and MI at 30 days.

30-Day Outcomes vs Preoperative NT-proBNP Level Below 100 pg/mL

The risks of the individual endpoints of myocardial injury, MI, all-cause mortality, and vascular death were also directly associated with increased preoperative NT-proBNP levels.

When NT-proBNP values were added to the Revised Cardiac Risk Index (RCRI) for patients with and without events, 21.4% and 26.4%, respectively, required a risk reclassification. This resulted in a net absolute reclassification improvement of 258 per 1,000 patients.

The results were maintained in sensitivity analyses looking at where NT-proBNP samples were evaluated (local lab versus shipped out) and also excluding patients with missing RCRI data.

Although Devereaux said he expected NT-proBNP would improve risk prediction, he was “very pleased and a bit surprised with how strongly it did.” As opposed to noninvasive cardiac testing, moreover, NT-proBNP “not only improved risk prediction among patients that were going to have events beyond the clinical information, it also improved risk prediction among the patients who were not going to have events, and that's not that common out of prognostic tests.”

Biomarker testing is also unique in that it places patients into categories of risk as opposed to taking a binary approach to calculating whether an event might happen. “What you're seeing with NT-proBNP is that very quickly you can put patients in big categories of risk, and that's also very helpful in terms of being able to have an impact in terms of managing patients because it's not just affecting one in 1,000, you're putting people into categories and differentiating them very quickly,” Devereaux said.

‘Major Step Forward’

In an accompanying editorial, Arman Qamar, MD, MPH, and Sripal Bangalore, MD, MHA (both of New York University Grossman School of Medicine, New York, NY), write that “the findings by Duceppe and colleagues are not surprising and demonstrate the biological underpinnings of NT-proBNP. Nonetheless, this study is a major step forward in advancing the use of biomarkers for preoperative cardiac risk assessment.”

While individualized and precise preoperative cardiac risk assessment is paramount prior to every elective noncardiac surgery and there is “unquestionable evidence about the prognostic significance of NT-proBNP in preoperative risk stratification,” the editorialists note that “these breakthroughs have not translated into routine clinical practice.”

What remains to be seen—and what may sway clinical practice—would be evidence showing that NT-proBNP-driven perioperative management reduces the risk for cardiovascular events, Qamar and Bangalore write. “The role of biomarkers in routine preoperative cardiac risk stratification is still in its infancy and further study is needed. This field is wide open to investigation to find a suitable position for biomarkers in this setting; for example, a randomized trial of biomarker-guided preoperative risk assessment versus RCRI alone may answer whether this approach results in meaningful improvement in outcomes. Until then, data support the use of NT-proBNP to personalize cardiac risk stratification in patients having noncardiac surgery.”

Devereaux agreed regarding the need for further research linking NT-proBNP levels and cardiac outcomes, adding that the ongoing large, international, randomized POISE-3 study might give better answers. Only patients with NT-proBNP above 200 ng/L will be included in this study and “we’re seeing how we might be able to prevent major bleeding and cardiovascular events with patients who have preoperative elevated troponins, based upon ways of managing blood pressure medications and also an antifibrinolytic drug. We also have ideas about how we might be able to decrease NT-proBNP in the coming period of time after surgery in patients with these NT-proBNP values that we hope to study, that hopefully can once again improve intermediate to long-term outcomes for these patients.”