Exploring the association of erythrocytic NO-ferroheme, a surrogate marker of endothelial function with perioperative cardiovascular events in low/intermediate risk patients undergoing elective non-cardiac surgery

• DOI: 10.1007/s44254-025-00096-4
• Publication Date: 2025-04-09T12:09:06Z
• Authors: Hasnae Boughaleb; Jerome Linden; Arvind Soni; Nathalie Fabian; Irina Lobysheva; Virginie Montiel; Mona Momeni; Marie-Agnès Docquier; Annie Robert; Nancy Van Overstr...; Jean-Luc Balligand
• Keywords: Surrogate endpoint

Abstract Purpose Pre-operative assessment of cardiovascular risk currently relies on scores, such as the American Society Anesthesiologists (ASA) score, biased towards high-risk, but neglecting middle/lower patients. Endothelial dysfunction is a precursor to events (CVEs), due impaired nitric oxide (NO) bioavailability. We previously showed that erythrocytic NO-ferroheme including 5-coordinated NO-heme-α-hemoglobin (HbNO), complex between NO and deoxyhemoglobin correlates with endothelial function assessed by digital tonometry. The aim this study was evaluate if HbNO associated different factors explore its association CVE in patients undergoing elective non-cardiac surgery. Methods conducted prospective, monocentric adult scheduled for At preoperative visit, blood samples were collected, erythrocytes isolated measure baseline levels, along other biomarkers routinely used pre-operative factors. signals quantified using electron paramagnetic resonance spectroscopy. Follow-up visits data analysis electronic health records at 1-, 3-, 6- 12- months postoperatively. primary endpoint occurrence composite CVE, arrhythmias, chest pain/unstable angina, myocardial infarction/ischemia, pulmonary edema, embolism, stroke, deep venous thrombosis, cardiac failure death any cause. Results Between November 2019 June 2022, 2,500 screened 1,066 underwent an Among kept final analysis, 23 subjects developed peri-operative up 30 days after surgery ( p- 30d CVE). Linear regression revealed several independent significantly correlated hemoglobin, anticoagulant usage, smoking status. Patients who exhibited lower mean levels (124.2 ± 96.6 nM) compared those did not (154.8 104.1 nM; p = 0.028). Using threshold 124 nM HbNO, below cutoff (HbNO < increased (OR [95% CI] 4.21 [1.55–11.41]), classification ASA III or higher 3.23 [1.38–7.59]). However, excluding high priori, remained 5.52 [1.57–19.33]) while ASA-score no longer significant 0.89 [0.20–3.97]). Conclusion In surgery, known factors, active independently negatively HbNO. without severe comorbidities, despite limited number CVEs observed, under positively score CVE. measurements could help improve evaluation low/intermediate Trial registration Registered ClinicalTrials.gov 19, (NCT03994900).