Serum Levels of FGF21, β-Klotho, and BDNF in Stable Coronary Artery Disease Patients With Depressive Symptoms: A Cross-Sectional Single-Center Study

Abstract

Background: The incidence of depressive symptoms (DS) in patients with stable coronary artery disease (SCAD) is significantly higher than those in healthy population, and that DS are independent risk factors for cardiovascular events. Previous studies have reported that fibroblast growth factor 21 (FGF21), β-klotho, mature brain-derived neurotrophic factor (mBDNF), and BDNF precursor (proBDNF) play important roles in the pathogenesis and treatment of coronary heart disease and depression. With this in mind, the present study aimed to clarify the relationship between FGF21, β-klotho, mBDNF, and proBDNF and SCAD with comorbid depression, in addition to also exploring the underlying mechanisms of these disease processes.Methods: A total of 116 patients with SCAD and 45 healthy controls were recruited. Patients with SCAD were further divided into two subgroups based on the Zung Self-Rating Depression Scale (SDS), which were characterized as those with no DS (NDS) and those with DS. Baseline data were collected, and serum levels of FGF21, β-klotho, mBDNF, and proBDNF were determined.Results: In SCAD patients, Gensini scores—denoting the degree of coronary arteriostenosis—were significantly greater in the DS group than in the NDS group. There was also a positive correlation between the Gensini scores and the SDS scores. Patients in the SCAD group demonstrated a lower serum FGF21. Serum β-klotho, mBDNF, and mBDNF/proBDNF were also significantly lower in the DS group than in the NDS group. Furthermore, β-klotho and mBDNF were negatively correlated with the SDS scores. Additionally, SCAD patients were divided into lower- and higher-level groups using hierarchical cluster analysis, with the results highlighting that patients in the lower mBDNF group had a higher incidence of DS.Conclusions: The depression score was positively correlated with the severity of coronary artery stenosis, and serum FGF21, β-klotho, mBDNF, and proBDNF were closely related to the development of DS in patients with SCAD. These observations suggest FGF21, β-klotho, mBDNF, and proBDNF as potential diagnostic and/or therapeutic targets for SCAD with co-morbid depression.

Coronary Heart Disease and Depression or Anxiety: A Bibliometric Analysis

“…They have been confirmed to have a high probability to be concomitant and to have an adverse effect on each other, pushing patients to undertake heavier burdens and suffering when they are afflicted by these diseases concurrently (Whooley et al, 2008 ). On the one hand, patients with CHD are more likely to suffer from mental disorders because they usually endure unpleasant symptoms like angina without warning and are required to take several kinds of medications for their whole life, resulting in negative emotions like anxiety or depression (Colquhoun et al, 2013 ; Wu et al, 2021 ). To be concrete, 20–30% of patients with heart diseases are diagnosed with anxiety or depression (Larsen et al, 2016 ).…”

Commentary: Serum Biomarkers Are Potential Diagnosis and Treatment Targets for Depressive Symptoms in Patients With Cardiovascular Diseases

“…Sigma-1 receptor agonists such as endogenous neurosteroid dehydroepiandosterone (DHEA) and selective serotonin reuptake inhibitors (SSRIs) have shown potent cardio-protective and antidepressant effects. In this study, Wu et al ( 4 ) firstly found that serum β-klotho in the depression group was significantly reduced, and that β-klotho was negatively correlated with the depression score. However, the detailed mechanisms remain to be identified.…”

“…However, the detailed mechanisms remain to be identified. Also, Wu et al ( 4 ) found that serum mBDNF levels were decreased in SCAD patients, and that mBDNF level and mBDNF/proBDNF ratio in the depression group were significantly decreased. More importantly, serum mBDNF levels were negatively correlated with SDS score.…”

“…However, the comorbidity of CVDs and depression still lacks effective objective diagnostic indicators. This is the question that Wu et al ( 4 ) tried to answer in this issue of Frontiers in Psychiatry ( Interplay of Stress, Pain and Psychiatric Diseases ). The authors recruited 116 patients with stable coronary artery disease (SCAD) and 45 healthy controls.…”

“…BDNF is an essential member of the neurotrophic factor family, regulating the development and plasticity of neurons. Notably, BDNF as a clue to explore potential biomarkers of cardiovascular diseases comorbid depression has been reported ( 4 , 7 ). Plasminogen activator inhibitor-1 (PAI-1) could act as a mediator of depression-induced CVDs through sleep disorder, adiposity, BDNF metabolism, systemic inflammation, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation.…”