Biomarkers Show Higher Risks in Repeated Vascular Surgery Patients

Author: Michael Vlessides

Anesthesiology News

Repetitive surgery is associated with myocardial injury in vascular patients, a German research team has found. Of note, the researchers also found that pentraxin 3—a biomarker of plaque vulnerability—is increased before the second procedure.

Studies have shown that myocardial injury after noncardiac surgery is an independent risk factor for 30-day mortality (Anesthesiology 2014;120[3]:564-578). Although the underlying mechanisms for this association are largely unknown, animal models have demonstrated that surgery combined with blood loss promotes progression of atherosclerotic lesions and plaque destabilization (Dis Model Mech 2015;8[9]:1071-1080).

“So we asked ourselves if perioperative stress under repetitive surgery increases patients’ risk of myocardial injury and/or plaque vulnerability,” said Henrike Janssen, MD, an anesthesiology resident at Heidelberg University Hospital, in Germany.

Pentraxin 3 was measured using ELISA (R&D Systems). N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured preoperatively, and high-sensitive cardiac troponin T (hs-cTNT) was measured both preoperatively and postoperatively. Additional third-generation cardiac troponin T (cTNT) or hs-cTNT measurements were prompted on clinical suspicion for acute coronary syndrome. Myocardial injury after noncardiac surgery was defined as any new hs-cTNT of 50 ng/L or higher, or third-generation cTNT more than 30 ng/L.

Rising Cardiovascular Risk

As Dr. Janssen reported at the 2018 annual meeting of the International Anesthesia Research Society (abstract CA79), preoperative and postoperative blood sample data were available for 37 patients (80% male; median age, 71 years). The median time between surgeries was 61 days (range, 45-185 days). There were no significant differences in preoperative medications or risk factors between interventions.

“We had 17 patients who underwent carotid endarterectomy twice,” Dr. Janssen added. “We also wanted to see if there was plaque vulnerability on the physiological side. In doing so, we saw a decrease in FOXP3-positive cells in the lesions of the second surgical procedure. And if you look at the literature, low numbers of regulatory T-cells in the atherosclerotic lesions indicate plaque vulnerability.”

One patient experienced myocardial injury after the first surgery, while this occurred in five patients after the second surgery (P<0.05).

Given these findings, the investigators urged their peers to recognize the elevated cardiovascular risk associated with repetitive operations. They acknowledged, however, that future research should determine potential associations between plaque vulnerability and cardiac risk, as well as the potential relationship of the time interval between surgeries to myocardial injuries.

“Is there a time course where the pentraxin 3 marker starts to trend down toward normal?” asked session moderator John D. Mitchell, MD, an associate professor of anesthesia at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.

“I would imagine the push-pull would be that if you know someone has bilateral carotid disease and there’s a higher risk of stroke in the intervening period between the first and second carotid surgery, does that mean you should operate sooner, even though the pentraxin 3 level is higher?” Dr. Mitchell asked. “Or should we wait longer until the level drops again?”

“The problem is that if you were to design a study for the assessment of histology, it would take a very long time,” Dr. Janssen replied. “It would be interesting to look at not just vascular surgery, but all cardiovascular risk patients who undergo repetitive surgical procedures outside of infectious reasons. I think this is important work already, but it would be interesting to be able determine the safe window for performing the second operation.”