Decline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events

Abstract

Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09-3.15, p = 0.02] and 2.21 [95% CI 1.22-4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.

Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

“…Reduced level of BChE has been observed in the last trimester of pregnancy 30. Decreased cholinergic status has been reported in burn patients31 and is associated with an increased risk for MACE32 and presence of carcinoma 33. Thus, only a combined diagnostic approach, comprising various laboratory tests and clinical examinations would identify the most effective treatment decision in the therapy of acute inflammation.…”

Review: Morphofunctional and biochemical markers of stress in sea urchin life stages exposed to engineered nanoparticles

“…AChE activity has been thoroughly investigated in relation to human health/stress conditions by the group of Soreq (Sklan et al, ; Arbel et al, ; Nadorp and Soreq, ), and in particular in inflammation‐related diseases, such as tumor genesis, Alzheimer, and in neurotoxic outcomes from environmental strikes, poisoning, etc.…”

Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis

“…It is best known for inactivating succinylcholine, a muscle relaxant used to facilitate abdominal surgery but endangers patients with “atypical BChE” that hydrolyzes it poorly. Although some BChE genetic variants are associated with elevated risk of cardiac death [1, 2] or early-onset Alzheimer’s disease [3], this enzyme was not known to play a direct role in mammalian physiology. But in 2004, De Vriese reported that BChE is capable of hydrolyzing the acylated peptide known as “ghrelin,” which stimulates hunger and food-seeking [4].…”