Characteristics of peripheral blood cells are independently related to major adverse cardiovascular events after carotid endarterectomy

L Malin Overmars; Joost M Mekke; Wouter W van Solinge; Saskia C A De Jager; Cornelia A R Hulsbergen-Veelken; Imo E Hoefer; Dominique P V de Kleijn; Gert J de Borst; Sander W van der Laan; Saskia Haitjema

doi:10.1016/j.athplu.2023.05.003

Characteristics of peripheral blood cells are independently related to major adverse cardiovascular events after carotid endarterectomy

Atheroscler Plus. 2023 Jun 1:52:32-40. doi: 10.1016/j.athplu.2023.05.003. eCollection 2023 Jun.

Affiliations

¹ Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
² Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
³ Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁴ Netherlands Heart Institute, Moreelsepark 1, 3511 EP, Utrecht, the Netherlands.

Abstract

Background and aims: Patients who underwent carotid endarterectomy (CEA) still have a residual risk of 13% of developing a major adverse cardiovascular event (MACE) within 3 years. Inflammatory processes leading up to MACE are not fully understood. Therefore, we examined blood cell characteristics (BCCs), possibly reflecting inflammatory processes, in relation to MACE to identify BCCs that may contribute to an increased risk.

Methods: We analyzed 75 pretreatment BCCs from the Sapphire analyzer, and clinical data from the Athero-Express biobank in relation to MACE after CEA using Random Survival Forests, and a Generalized Additive Survival Model. To understand biological mechanisms, we related the identified variables to intraplaque hemorrhage (IPH).

Results: Of 783 patients, 97 (12%) developed MACE within 3 years after CEA. Red blood cell distribution width (RDW) (HR 1.23 [1.02, 1.68], p = 0.022), CV of lymphocyte size (LACV) (HR 0.78 [0.63, 0.99], p = 0.043), neutrophil complexity of the intracellular structure (NIMN) (HR 0.80 [0.64, 0.98], p = 0.033), mean neutrophil size (NAMN) (HR 0.67 [0.55, 0.83], p < 0.001), mean corpuscular volume (MCV) (HR 1.35 [1.09, 1.66], p = 0.005), eGFR (HR 0.65 [0.52, 0.80], p < 0.001); and HDL-cholesterol (HR 0.62 [0.45, 0.85], p = 0.003) were related to MACE. NAMN was related to IPH (OR 0.83 [0.71-0.98], p = 0.02).

Conclusions: This is the first study to present a higher RDW and MCV and lower LACV, NIMN and NAMN as biomarkers reflecting inflammatory processes that may contribute to an increased risk of MACE after CEA.

Keywords: Blood cell characteristics; Carotid endarterectomy; Hematology; Inflammation; Intraplaque hemorrhage; Machine learning; Major adverse cardiovascular events; Routine care data.