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.

BACKGROUND: The 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. METHODS: Plasma 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. RESULTS: Among 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(ß) = 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(ß) = 0.114, 95%-CI = 0.023-0.566, p = 0.008). CONCLUSIONS: Our 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.

Higher plasma levels of MR-pro-atrial natriuretic peptide are linked to less anxiety: results from the observational DIAST-CHF study.

AIMS: Growing evidence suggests that natriuretic peptides play a role in the neurobiology of anxiety. In the present study, we investigated whether in patients with cardiovascular risk factors higher plasma levels of natriuretic peptides are linked to reduced anxiety. METHODS: A total of 1,360 patients from the observational DIAST-CHF study (mean age 65.9 ± 8.2 years, 48.7 % males, mean left ventricular ejection fraction 60.0 ± 8.2 %) with risk factors for diastolic heart failure were included. Study participants underwent physical examination, echocardiography, and assessment of anxiety using the Hospital Anxiety and Depression Scale (HADS). In addition, plasma concentrations of natriuretic peptides were measured. RESULTS: Among the total study population, there were n = 117 patients (8.6 %) with HADS anxiety scores above the cut-off (≥11) suggestive of clinically relevant anxiety. In bivariate analyses, we found a significant inverse association between elevated HADS anxiety and log-transformed mid-regional pro-atrial natriuretic peptide (MR-proANP) (p < 0.001) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) (p = 0.008). Logistic regression models adjusted for sex, age, body mass index, and Framingham score confirmed that plasma MR-proANP (exp(ß) = 0.35, 95 % confidence interval [95 % CI] 0.14-0.92, p = 0.032) concentrations were significantly and inversely associated with clinically relevant anxiety, while NT-proBNP (exp(ß) = 0.67, 95 % CI 0.41-1.07, p = 0.094) failed to reach the significance level in independently predicting anxiety. CONCLUSIONS: In our study population of outpatients with cardiovascular risk factors, plasma concentrations of MR-proANP were negatively and independently related to clinically relevant anxiety. Further investigations are required to search for possible anxiolytic effects of this circulating natriuretic peptide in medical outpatients with cardiovascular risk factors for diastolic dysfunction.