Cardiac Biomarkers Associated with Worse Outcomes Following Cardiac Surgery

Elevated levels of soluble ST2 (sST-2) and N-terminal prohormone of BNP (NT-proBNP) may be correlated with lower survival rates after cardiac surgery, new research suggests.

“Biomarkers have demonstrated their value in other fields of medicine in terms of disease detection, surveillance, and prediction, and yet, we haven’t fully explored their utility in cardiovascular outcomes,” said study author Niveditta Ramkumar, a PhD student at the Dartmouth Institute for Health Policy and Clinical Practice, who presented the findings at the 65^th Annual Meeting & Exhibition of the Southern Thoracic Surgical Association.

Ramkumar and colleagues assessed cardiac surgery patients from 2004 to 2007, who were enrolled in the Northern New England Cardiovascular Disease Study Group Registry. They evaluated pre- and post-operative serum biomarkers, using Kaplan-Meier survival analysis and Cox regression models adjusted for variables in the STS’s ASCERT long-term survival calculator to make a connection between biomarker levels and survival. The researchers categorized pre- and postoperative serum biomarker levels into quartiles (quartiles 2 and 3 were found to have similar survival and were therefore combined into one category, the authors noted).

The final analyses included 1,648 patients (78% men; mean age, 65), who were followed for a median eight years; 267 patients died. Ten-year survival rate was 86%. In Kaplan-Meier survival analysis, researchers saw significant differences based on pre- and post-operative biomarker levels (P < 0.001).

Researchers adjusted for age, weight, height, creatinine, ejection fraction, mean aortic gradient, sex, ethnicity, diabetes, cerebrovascular disease, cigarette smoking, congestive heart failure class, prior cardiac operation, cardia status, number of diseased coronary vessels, myocardial infarction, and valve insufficiency. In their adjusted analyses, the reference preoperative sST-2 level was < 3.195 ng/mL; 10% of these patients died. Patients with sST-2 levels 3.195 to 5.87 ng/mL before surgery had a 1.36 hazard ratio (HR) in comparison; 15% of these patients died. Preoperative sST-2 levels > 5.87 ng/mL had a 1.52 HR compared with the reference point, and 22% of these patients died. Postoperatively, the reference was < 26.366 ng/mL, and 7.5% of these patients died. While sST-2 levels 26.366 to 83.866 ng/mL were not correlated with increased mortality (HR 0.93; 14% of patients died), sST-2 levels elevated beyond 83.866 ng/mL indicated a 1.66 HR (27% of patients died).

In preoperative NT-proBNP analyses, the reference point was < 1.005 ng/mL (3.9% of patients died). NT-proBNP levels 1.005 to 5.71 ng/mL and > 5.748 ng/mL prior to operation had a HR of 1.36 and 1.52, respectively (15% and 22%, respectively, of patients died). Postoperative reference measurement for NT-proBNP was < 7.952 ng/mL; 6.5% of these patients died. Patients with NT-proBNP levels 7.955 to 25.202 ng/mL following operation were not at a significantly increased risk of death (HR=0.81; 12% of patients died), but patients with NT-proBNP levels > 25.202 ng/mL after surgery had hazard ratio of 1.46  (33% of patients died).

Study limitations included its primarily older patient population, limiting the generalizability of the results to younger patients. The patients also underwent surgery between 2004 and 2007, “and cardiac surgery practices have changed since then,” Ramkumar said. The researchers also looked at all-cause, not disease-specific, mortality, “so we aren’t quite sure how prognostic our biomarkers would be.”

“Elevated pre- and post-operative levels of sST-2 or NT-proBNP are associated with increased risk of worse survival after cardiac surgery,” the study authors concluded. “These biomarkers can be used for risk stratification or estimating postsurgical prognosis”

Ramkumar noted that “our next steps would be to study these associations in a more modern cohort and potentially establish thresholds for risk stratification using these biomarkers.”