Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study

Abstract

BackgroundThe role of endothelin-1 (ET-1) in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1) is linked to anxiety.MethodsPlasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2%) who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire.ResultsAmong the total study cohort (n = 1,410), there were 118 subjects (8.4%) with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013). In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β) = 0.247, 95%-confidence interval [95%-CI] = 0.067–0.914, p = 0.036). Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β) = 0.114, 95%-CI = 0.023–0.566, p = 0.008).ConclusionsOur data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.

Ansiedade e depressão em pacientes com doença arterial periférica internados em hospital terciário

“…With regard to depression, the results of the present study were in line with the literature, 1,17,30,35,36 since the profile of these patients was predominantly female, surviving on the minimum wage or less, and married or in a stable relationship. This was also the case with the patients with anxiety, contradicting both the study that found a higher prevalence in women with no sexual partner, since divorced women were at higher risk of suicide because of depression than those who were married or widowed, 14 and also one that found a discrete prevalence among males and another that found equal frequency in both sexes.…”

“…1,9,15,[17][18][19]35,36 Another point that it is indispensable to discuss is that both anxiety and depression are risk factors for CVD, such as AMI, stroke, and PAD. 1,15,17,30,[34][35][36][37][38] This could be because patients with anxiety/depression tend to have a less healthy lifestyle, with dietary errors and without physical exercise, 33,39 as was observed in our sample, the great majority of whom did not do regular physical exercise. However, in contrast to some other studies, 33,36 this factor did not affect the presence of depression.…”

“…Elderly women were diagnosed with GAD and with depressive disorder more frequently, as has been detected in some previous studies. 5,14,30,31 However, Bhutani et al 32 conducted a study investigating the risk of these disorders among patients amputated because of external causes and found that elderly patients had less anxiety and depression than younger patients, since they had lower expectations and a lower probability of developing emotional disorders.…”

Higher galectin-3 levels are independently associated with lower anxiety in patients with risk factors for heart failure

“…Beside its prognostic value for heart failure patients [ 20 , 49 , 50 ], our data from the Diast-CHF study suggest an unknown mechanism of galectin-3 in the regulation of anxiety also in humans. Thus, this galactoside-binding lectin may be added to the growing list of peptides functioning as prognostic biomarkers of heart failure (NT-proBNP, NT-proANP, MR-proANP, CT-ET-1, CT-proAVP, and MR-pro-adrenomedullin) that, in addition, negatively associate with anxiety [ 13 – 16 , 51 , 52 ].…”

Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety

“…Endothelin-1 (ET1) is a 21-amino-acid peptide and a potent vasoconstrictor that was first isolated from the supernatant of cultured porcine aortic endothelial cells 15 . Although many previous human studies have shown links between ET1 and diseases such as arterial hypertension and renal disease 16 – 19 , recent patient data has shown possible connections between ET1 and anxiety 20 , 21 and between ET1 and depression 22 . ET1 is widely distributed in the CNS and acts on two distinct G protein-coupled receptors: the ETA receptor (ETAR) and the ETB receptor (ETBR) subtypes 16 , 23 – 25 .…”